What Happens to the Transcript Rna Before It Leaves the Nucleus
Traffic. Author manuscript; bachelor in PMC 2013 Jul 5.
Published in final edited grade as:
PMCID: PMC3702165
NIHMSID: NIHMS240257
Messenger RNA Export from the Nucleus: A Series of Molecular Wardrobe Changes
Abstract
The advent of the nucleus during the evolutionary evolution of the eukaryotic cell necessitated the development of a transport organisation to convey messenger RNA (mRNA) from the site of transcription in the nucleus to ribosomes in the cytoplasm. In this review, we highlight components of each pace in mRNA biogenesis, from transcription to processing, that are coupled with mRNA export from the nucleus. We also review the machinery past which proteins from one footstep in the mRNA associates line are replaced by those required for the next. These 'molecular wardrobe changes' announced to be key steps in facilitating the rapid and efficient nuclear export of mRNA transcripts.
Keywords: 3′-cease processing, export factor adaptor proteins, Mex67/TAP, mRNA, mRNA-binding proteins, mRNA consign, mRNA processing
Before messenger RNA (mRNA) transcripts are exported from the nucleus, they must first be extensively processed. Each of these processing events, including improver of a v′-cap, the splicing out of introns, and 3′-end cleavage and polyadenylation, also as mRNA export itself, is tightly regulated allowing for plasticity in modulating gene expression (1). Particular aspects of transcription, as well every bit each of these processing events, are coupled with mRNA export, making the unabridged process one dynamic assembly line from start to finish. This assembly line tin can produce thousands of copies of a single transcript constitutively or only several copies of a transcript once during the development of an organism. The complex regulatory system that dictates when and where a gene is expressed is controlled not only past a complicated series of transcriptional regulators but also by an equally elaborate network of RNA-binding proteins that acquaintance with the mRNA transcript during postal service-transcriptional events (Encounter Table 1 for a summary of factors). These mRNA-bounden proteins function in diverse processes ranging from splicing to cytoplasmic RNA localization, but collectively they dictate the fate of each transcript. Like any associates line, each sequential step constitutes a function that is a necessary prerequisite for the next.
Tabular array 1
Protein factors implicated in mRNA export from the nucleus.
| Southward. cerevisiae protein | Higher eukaryotic orthologue | RNA accumulation in nucleus?a | Office in mRNA export functions | Other described | References |
|---|---|---|---|---|---|
| ain either yeast cells expressing mutant proteins or higher eukaryotic cells depleted for the specified factor, does poly(A) or heat shock RNA accumulate in the nucleus as detected by fluorescence in situ hybridization (FISH)? | |||||
| bN/A: information on RNA accumulation is, to the best of our knowledge, not available. | |||||
| cAs specified, either poly(A) RNA or rut shock RNA accumulates in the nucleus, only not both. | |||||
| dMutants accumulate poly(A) RNA but, to the best of our noesis, nuclear accumulation of rut shock RNA has non been tested. | |||||
| Hpr1 | hHpr1 | Poly(A) and heat shock RNA | Component of yeast/human TREX and direct recruiter of Mex67 (yHpr1) | Transcriptional Elongation (yTREX), Genome Stability (yHpr1) | (7,8,18,ten) |
| Tho2 | hTho2 | Poly(A) and estrus shock RNA | Component of yeast/homo TREX | THO complex member | (7,8,x) |
| Mft1 | — | Poly(A) and estrus shock RNA | Component of yTREX | THO complex member | (7,viii,x,77) |
| Thp2 | — | Poly(A) and estrus shock RNA | Component of yTREX | THO complex member | (7,eight,10) |
| Tex1 | hTex1 | Northward/Ab | Component of yTREX | THO circuitous member | (58,78) |
| — | Thoc5/fSAP79/FMIP | Heat shock RNA onlyc | Component of hTREX, required for consign of heat shock RNA | Mail-transcriptional regulation of genes involved in macrophage/adipocyte differentiation | (58,65,79,80) |
| — | Thoc6/fSAP35 | Due north/Ab | Component of hTREX | — | (58) |
| — | Thoc7/fSAP24 | N/Ab | Component of hTREX | — | (58) |
| Sub2 | UAP56 | Poly(A) and oestrus shock RNA | Yra1 adaptor protein | ATP-dependent helicase, function in splicing | (12,13,81) |
| Yra1 | Aly/REF | Poly(A) and oestrus daze RNA | Mex67 adaptor protein | RNA-annealing activity | (v,half dozen,14,15) |
| Mex67:Mtr2 | TAP:p15/Nxf1: Nxt1 | Poly(A) and estrus stupor RNA | Chief mRNA consign cistron; contacts mRNA (directly and via adaptors) and nucleoporins | Nuclear consign of 60s ribosomes | (two,three,29,82,83) |
| Pcf11 | Pcf11 | Poly(A) RNAd | Yra1 adaptor poly peptide | mRNA iii′-end germination | (19,34,84,85) |
| Rna14 | CstF77 | Poly(A) and oestrus shock RNA | — | mRNA three′-end formation | (34,36,84,85) |
| Rna15 | CstF64 | Poly(A) and heat shock RNA | — | mRNA three′-end germination | (34,36,84,85) |
| Hrp1 | — | Heat shock RNA onlyc | — | mRNA three′-end formation, mRNA transcript stability | (35,65,79,84) |
| Pap1 | Pap1 | Poly(A) and heat shock RNA | — | Poly(A) polymerase/mRNA 3′- cease formation | (34,84,85) |
| Nab2 | ZC3H14 | Poly(A) RNAd | Possible Mex67 adaptor protein | mRNA processing/3′- finish formation | (39,49,55,86) |
| Npl3 | — | Poly(A) RNA onlyc | Mex67 adaptor protein | mRNA 3′-end cleavage and polyadenylation site selection, promotes pre-mRNA splicing | (21–25) |
| Dbp5/Rat8 | hDbp5/DDX19 | Poly(A) and heat shock RNA | mRNP remodeling in the cytoplasm following nuclear export | Interacts with transcription and translation-termination factors | (72,74,75,87) |
| Gle1 | hGle1 | Poly(A) and heat shock RNA | Activator of Dbp5 (in combination with hNup214/yNup159) | Regulation of translation | (88–93) |
| Thp1 | — | Poly(A) and heat stupor RNA | Component of yTREX2 complex involved in nuclear export of mRNA | Regulation of genomic integrity | (78,94–97) |
| Sac3 | GANP/Shd1 | Poly(A) and oestrus shock RNA | Component of yTREX2 complex involved in nuclear export of mRNA | Regulation of genomic integrity | (78,95–98) |
| Sus1 | DC6/Eny2 | Poly(A) RNAd | Component of yTREX2 complex involved in nuclear export of mRNA, possible 'span' protein between transcription and mRNA consign | Component of SAGA histone modification circuitous, regulation of genomic integrity | (95,98–100) |
| Cdc31 | CETN3 | Poly(A) RNAd | Component of yTREX2 circuitous involved in nuclear export of mRNA | Duplication of microtubule-organizing centers | (95,96,98, 101,102) |
In order for a transcript to leave the transcription 'assembly line' in the nucleus and exist delivered to ribosomes in the cytoplasm, it must first recruit mRNA export factors. Conventionally, export factors have been divers based on their chapters to demark both the RNA transcript and components of the nuclear pore complex (NPC), and they are, therefore, thought to actively escort mRNA transcripts through the NPC and out of the nucleus. One of the overarching themes in mRNA export is the use of adaptor proteins to recruit these export factors. Although consign receptors tin bind directly to mRNA transcripts (2–4), their recruitment to mature export-competent mRNA transcripts is thought to be profoundly enhanced when they are recruited via adaptor proteins (v,vi). These adaptor proteins are hypothesized to specifically recognize RNA sequences to signal that a particular processing footstep is complete, and consequently that the transcript is competent for export to the cytoplasm. Many of these proteins function not but as adaptors but too as important components of other processes, such as splicing or 3′-cease processing; hence these processes are 'coupled' with mRNA export via these adaptor proteins. Although many of the individual proteins involved in mRNA biogenesis are highly conserved from yeast to higher eukaryotes, the particular processes that are coupled with nuclear export are more divergent. In Saccharomyces cerevisiae, the primary mRNA export cistron, Mex67 and its heterodimeric partner Mtr2, appears to be recruited through a transcription- and 3′-end processing-dependent mechanism. In higher eukaryotes, however, the recruitment of the Mex67:Mtr2 orthologues, chosen TAP:p15 (or NXF1:NXT1), to mature mRNA transcripts appears to exist dependent upon 5′-cap add-on and splicing.
Studies using the budding yeast S. cerevisiae as a model system have provided a valuable initial framework for understanding the process of mRNA export; elegant studies performed in college eukaryotes have offered farther insight. Throughout this review, we volition highlight the mechanisms by which eukaryotic cells couple transcription and processing to mRNA export from the nucleus. We also focus on the complex molecular displacements that occur throughout the life cycle of an mRNA transcript and the mechanisms by which these 'molecular wardrobe changes' facilitate coupling of transcription and processing to mRNA export.
Coupling Transcription to mRNA Export from the Nucleus
References
During transcription and before mRNA export, adaptor proteins are deposited forth nascent transcripts. Recent studies take shown that a multi-protein complex, termed the transcription and export (TREX) complex, is assembled upon the nascent transcript during transcription and is a critical component in determining the efficiency of mRNA export from the nucleus (7–9). Once deposited, components of this circuitous recruit adaptor proteins to the newly synthesized transcript. The S. cerevisiae TREX circuitous consists of the mRNA export adaptor proteins, Sub2 and Yra1, and components of the THO circuitous (Hpr1, Mft1, Thp2 and Tho2) (seven–10). Sub2, and its mammalian counterpart UAP56, are putative ATP-dependent helicases that role in splicing and export (11–13). Yra1 (Aly/REF in higher eukaryotes) has also been implicated in pre-mRNA metabolism (xiv) and mRNA export (5,15). The THO circuitous components, several of which are conserved in college eukaryotes, are required for a wide variety of processes including transcriptional elongation (16,17) and genome stability (16).
The S. cerevisiae THO component, Hpr1, is co-transcriptionally recruited to actively transcribed loci (10,18) and directly contacts the mRNA export adaptor protein, Sub2 (18). Furthermore, components of the THO complex tin exist co-purified with both Yra1 and Sub2 (10), although THO subunits do not straight interact with Yra1, suggesting that the interaction between THO and Yra1 is bridged past Sub2 (xviii). These data suggest a model (Effigy 1A) whereby THO components, specifically Hpr1, are recruited to actively transcribed loci and subsequently recruit Sub2 and Yra1. Yra1 tin and so serve equally an adaptor protein for the primary S. cerevisiae mRNA export factor, Mex67 (5,15). In order for this complicated recruitment scheme to function correctly, the transcript must undergo several 'molecular wardrobe changes' to properly recruit and afterwards displace these adaptor proteins. For example, Sub2 and Mex67 both interact with the same domain of Yra1 (10), suggesting that these interactions with Yra1 are mutually exclusive. This exclusivity is necessary to displace Sub2 from the transcripts when Yra1 recruits Mex67 (Effigy 1A). Yra1 directly interacts with Mex67 but does not exit the nucleus (five), suggesting that before Mex67 can escort transcripts through the NPC, Yra1 must first be removed.
Schematics illustrating possible mechanisms for recruitment of the Southward. cerevisiae mRNA export receptor, Mex67, to mRNA transcripts are shown. A) 'Classical' model of Mex67 recruitment. The principle mRNA consign heterodimer, Mex67:Mtr2, is recruited via directly interactions with Yra1 in a Sub2- and THO complex-dependent mode. THO complex members are initially deposited upon nascent transcripts via interactions with the C-last domain (CTD) of RNA polymerase II (RNA Politician Ii). Following THO deposition, Sub2 and Yra1 are recruited to the transcript. Finally, the heterodimeric complex of Mex67:Mtr2 is recruited via interactions between Yra1 and Mex67. Bounden of Mex67 to Yra1 displaces Sub2. B) Sub2/Yra1-contained recruitment of Mex67. The heterodimeric export receptor, Mex67:Mtr2, tin can also be recruited to mRNA transcripts via direct interactions with both components of the THO complex, Hpr1, and the RNA-binding poly peptide, Npl3. C) Revised 'classical' model of Mex67 recruitment. Mex67:Mtr2 is recruited to mRNA transcripts via interactions with 3′-end processing components. Although initial studies (five,fifteen) showed that Yra1 was recruited to transcripts directly via THO components and Sub2, more recent data suggest a revised model where Yra1 is initially recruited to the mRNA transcript via interactions with the 3′-end processing factor, Pcf11 (19) and later on transferred to the TREX complex via an interaction with Sub2. Yra1 then recruits Mex67 and transcripts are exported.
Although Sub2 directly interacts with both Hpr1 and Yra1 and likely bridges this interaction (18), boosted evidence suggests that both Yra1 and Mex67 can exist recruited to mRNA transcripts via alternative mechanisms (Effigy 1B) (19). Notably, several studies have shown that the Ubiquitin-associated (UBA) domain of Mex67 interacts with the THO component, Hpr1 (20), suggesting that the THO complex tin directly recruit Mex67 to mRNA transcripts independent of Yra1 and Sub2. In addition to THO complex-mediated recruitment, other RNA-bounden proteins tin can too recruit Mex67 to mRNA transcripts. In detail, the RNA-binding poly peptide Npl3 has been implicated in Mex67 recruitment to mRNA transcripts (21). Npl3 is an essential serine–arginine rich (SR) protein that is co-transcriptionally loaded onto nascent transcripts (22,23) and is required for proper nuclear export of poly(A) RNA (24). Interestingly, Npl3 plays roles in both polyadenylation site choice (22,25) and early recruitment of spliceosomal proteins to intron-containing transcripts (23), suggesting that these processes could exist coupled with Mex67 recruitment.
In improver to the alternative routes for Mex67 recruitment to mRNA transcripts, Yra1, one of the principle Mex67 adaptors, may itself have additional adaptors beyond the commonly accepted Sub2 helicase. Specifically, inactivation of a component of the 3′-end cleavage machinery, Pcf11, causes an approximately twofold reduction in recruitment of Yra1 to the actively transcribed PMA1 locus without affecting Sub2 recruitment. Yra1 interacts with components of the iii′-end cleavage machinery, including Pcf11 and Rna15 (19). Furthermore, Pcf11 and other components of the 3′-end processing machinery tin can exist recruited to actively transcribed loci via interaction with the C-terminal domain of RNA polymerase II (26–28). Together, these data advise a revised model (Figure 1C) in which Yra1 can be recruited to actively transcribed loci in a Sub2-contained manner via an interaction with the 3′-end processing machinery component, Pcf11. Yra1 is then transferred from Pcf11 to the TREX complex via an interaction with Sub2. Yra1, now bound to the mRNA transcript, recruits the mRNA export heterodimer, Mex67:Mtr2, and the mature mRNA can get out the nucleus.
Even though millions of distinct transcripts are constantly transcribed, most current models for mRNA export suggest that 1 heterodimeric receptor, Mex67:Mtr2 (TAP:p15 or NXF1:NXT1 in higher eukaryotes), transports all transcripts through the NPC into the cytoplasm. These models rely on the initial observation that Mex67:Mtr2 could demark to both RNA and nuclear pore components (ii,29). However, recent genome-wide studies raise the possibility that Mex67-dependent export is not the only route for mRNAs to exit the nucleus. Ane such study showed that Mex67 and Yra1 were bound to 1142 and 1002 transcripts, respectively. Notably, only 349 transcripts were institute in common among the pools of transcripts bound to each protein (thirty). This finding raises several interesting points. Starting time, Mex67 and Yra1 each associated with distinct classes of RNAs (30), suggesting that expression of functionally related RNAs, such as those that encode proteins required for cell wall biosynthesis, tin be postal service-transcriptionally co-ordinated by regulation of these RNA export factors (30). Interestingly, a split genome-broad written report investigating the transcripts associated with the S. cerevisiae RNA-bounden proteins, Npl3, Nab2 and Hrp1, showed that these proteins preferentially acquaintance with functionally distinct classes of RNAs (31), providing farther evidence that particular RNA-binding proteins associate with specific transcripts. Second, these genome-broad studies indicate that the Yra1 and Mex67-centric mRNA export model may not be applicable for all mRNA transcripts and suggest that other RNA-binding proteins and poly peptide complexes may actively facilitate mRNA export from the nucleus by interacting with both mRNA transcripts and nucleoporins (Nups).
Coupling 3′-End Formation and mRNA Export
Although at that place are some discrepancies between yeast and higher eukaryotes in three′-finish formation, the overall processes of cleavage and polyadenylation are remarkably conserved [reviewed by (32)]. The initial step in 3′-end formation involves the recognition of specific sequences inside the pre-mRNA 3′-untranslated region (three′-UTR) and cleavage of the transcript. Once the transcript has been cleaved, poly(A) polymerase (PAP) adds the 200–250 adenosines (70–xc adenosines in S. cerevisiae) that contain the poly(A) tail. In both budding yeast and mammalian cells, the poly(A) tail is jump past a complement of poly(A)-binding proteins (Pabs) (33). Although coupling of mRNA export and 3′-end processing is somewhat controversial in metazoans, in Southward. cerevisiae 3′-end processing has been more than straight implicated in mRNA export from the nucleus. Notably, mutations within several yeast iii′-end processing factors, including Rna14, Rna15, Pcf11 and Pap1 crusade aggregating of bulk poly(A) RNA in the nucleus (34–36). In addition, mutations in numerous Due south. cerevisiae mRNA export factors, including Mex67, Yra1, and the cytoplasmic NPC-associated helicase Dbp5 (see beneath), cause hyperpolyadenylation of transcripts (34,37). Components of the iii′-end processing machinery also genetically interact with mRNA export factors (38,39).
Several studies in S. cerevisiae have investigated the link between 3′-end processing and mRNA consign using reporter transcripts truncated by a hammerhead ribozyme rather than processed by the normal 3′-cleavage and polyadenylation machinery (xl,41). Hammerhead ribozymes are self-cleaving RNA sequences, which were originally isolated from institute viruses (42). RNA transcripts synthesized by RNA polymerase II that comprise a ribozyme sequence in lieu of a standard 3′-UTR are non polyadenylated efficiently and are too not efficiently exported from the nucleus (forty). Export of these ribozyme truncated reporter RNAs is not entirely blocked, nevertheless, every bit deletion of the gene encoding the cytoplasmic riboexonuclease, XRN1, results in an increase in cytoplasmic reporter RNA, suggesting that a fraction of these reporter transcripts exits the nucleus only is rapidly degraded considering of the absence of a poly(A) tail (40). Interestingly, export of these reporters is rescued past an encoded stretch of adenosines immediately upstream of the self-cleaving ribozyme sequence that mimics a poly(A) tail. This result suggests that although the presence of a poly(A) tail helps facilitate mRNA export from the nucleus, the poly(A) tail is not an absolute requirement. Indeed, TRP4 transcripts terminated at their 3′-ends by a hammerhead ribozyme can partially complement a trp4 deletion mutant, indicating that a fraction of these non-polyadenylated transcripts can exit the nucleus and be translated (43). Whether these ribozyme-terminated transcripts are exported by Mex67 and the canonical mRNA consign machinery or by components of some other RNA consign pathway remains unclear.
Although 3′-end formation appears to be coupled with mRNA export from the nucleus in S. cerevisiae(34,37,39,40), little information exists as to the actual concrete link between components of the 3′-finish processing machinery and mRNA consign factors. One candidate class of proteins consists of the Pabs. Pabs are conserved from yeast to higher eukaryotes and are important in the regulation of transcript polyadenylation, stability, translation and nuclear export (44). The well-nigh well-characterized Due south. cerevisiae Pab, Pab1, localizes to the cytoplasm at steady state and regulates both translation and mRNA stability (44). In addition, Pab1 shuttles into the nucleus (45,46) and regulates poly(A) tail length (47,48). This collection of observations, forth with the fact that mutations within Pab1 only show express effects on poly(A) RNA export (46), suggests that although Pab1 may enter the nucleus, its principle role is likely in the cytoplasm and not in coupling mRNA 3′-terminate formation to nuclear export. More probable candidate proteins that couple iii′-terminate processing and mRNA consign are nuclear Pabs, such as Due south. pombe Pab2 [PABN1 in higher eukaryotes (44)] or Southward. cerevisiae Nab2 [ZC3H14 in higher eukaryotes (49)]. Although Pab2 and its orthologue PABN1 bind specifically to polyadenosine RNA and attune polyadenylation (fifty,51), neither protein has been linked to mRNA export from the nucleus. A more than likely candidate Pab that couples mRNA 3′-cease processing to nuclear consign may exist Nab2, which binds specifically to polyadenosine RNA in vitro(49,52,53) and besides regulates poly(A) tail length (53,54). Nab2 mutants also prove nuclear accumulation of bulk poly(A) RNA (53,55) and genetically interact with both Mex67 (39,56) and Yra1 (57). Therefore, Nab2 could office equally a factor involved in 3′-end germination that serves as an adaptor for Mex67 recruitment to export-competent transcripts.
Coupling Splicing and mRNA Export from the Nucleus
References
Although both yeast and higher eukaryotes use a conserved set up of factors to facilitate the nuclear export of mRNA transcripts, the mechanisms that recruit these factors are somewhat divergent. In higher eukaryotes, where about transcripts are subject to splicing, mRNA consign receptors seem to be recruited to the 5′-end of transcripts in a splicing-dependent manner.
The human TREX (hTREX) complex contains the adaptor proteins UAP56 and Aly/REF, orthologues of budding yeast Sub2 and Yra1, respectively, as well every bit the human THO complex members, hHpr1, hTho2, Thoc5/fSAP79, Thoc6/fSAP35 and Thoc7/fSAP24 (58). Different their S. cerevisiae counterparts, hTREX constituents (including UAP56, Aly/REF and THO members) have not been straight linked to transcription but instead accept more directly been linked to the addition of the v′-7-methyl guanosine cap and the splicing out of introns (58–61). Early studies suggested that hTREX recruitment may be coupled with splicing because UAP56 co-purified with spliceosomal proteins, specifically U2AF65(62,63), and Aly/REF associates with the exon junction complex (EJC), a multi-protein complex deposited 20–24 nucleotides upstream of exon–exon junctions (64). hTREX components also preferentially associate with mRNA transcripts that have undergone splicing rather than artificial transcripts manufactured from complementary DNA (cDNA) constructs (60). Furthermore, Aly and Thoc5 colocalize with nuclear speckles, which are subnuclear domains thought to store processing factors and components of the spliceosome (58,61,65). Together, these results suggested that hTREX is associated with spliceosomes and potentially is recruited as a role of the EJC.
Interestingly, more contempo studies have shed some doubt on the idea that TREX is recruited to nascent transcripts as part of the spliceosome or the EJC in higher eukaryotes. In detail, both hTREX and Aly are recruited to the v′-stop of mRNA transcripts (58,60). Several hTREX components, including Aly, UAP56 and hTho2, interact with the cap-binding complex, which specifically recognizes the seven-methyl guanosine cap on the 5′-finish of mRNA transcripts (lx,66). In addition, recruitment of Aly and a component of the hTHO complex, hTho2, to decapped reporter transcripts is dramatically decreased compared with properly capped transcripts (lx). Moreover, eIF4A3, a component of the EJC, is recruited to capped and decapped transcripts equally well (60), suggesting that TREX recruitment is dependent upon the 5′-cap, whereas recruitment of the EJC is non. Equally the improver of a 5′-cap dramatically increases the efficiency of nuclear export of spliced transcripts (60), recruitment of hTREX, and thus mRNA export receptors, is highly likely to be dependent upon both capping and splicing.
Translocation Through the NPC
One time an mRNA transcript has been properly processed, packaged and has recruited the correct export receptors, the resulting mRNA ribonucleoprotein (mRNP) complex is translocated through NPCs to the cytoplasm. The NPC consists of several classes of Nups, including structural Nups and Nups-containing domains rich with phenylalanine–glycine (FG) repeats. FG-Nups line the interior cavity of the NPC and allow for regulated macromolecular transport in and out of the nucleus (67). Multiple hypotheses exist (68) as to the exact mechanism by which nuclear pores maintain cargo selectivity while still retaining the capacity to transport cargoes efficiently and rapidly. Mostly, these FG repeats are idea to extend into the central crenel of the NPC and grade multiple low affinity interactions with soluble ship factors, such as Mex67/TAP (2,29,67), as they transit the NPC. Interestingly, recent piece of work has shown that dissimilar transport receptors (i.east. mRNA export versus different pathways for protein import) may require different subsets of FG-Nups (three,67,69), suggesting that different transport receptors may take different routes through NPCs.
A Molecular Wardrobe Change Completes Nuclear Export
Throughout the associates line of mRNA processing that culminates in export from the nucleus, a multitude of different proteins acquaintance with the mRNA transcript (Figure 2). Initially, mRNA processing proteins are recruited to the nascent transcript during transcription via interactions with the C-terminal domain of RNA polymerase Two. Many of these processing factors are displaced following completion of processing or earlier export from the nucleus. Export factors then recognize the mature transcripts and convey them through the NPC to the cytoplasm. The export factors are subsequently displaced and factors that regulate the cytoplasmic destiny of the transcript bind. These cycles of protein displacement occur continually throughout the life bicycle of an mRNA transcript and help functionally according mRNA biogenesis. One of the best-characterized examples of this wheel of molecular deportation occurs immediately following translocation of the mRNP through the NPC. Upon reaching the cytoplasmic side of the NPC, the mRNP must undergo a pregnant remodeling upshot to replace nuclear consign factors with a new complement of proteins that regulate the cytoplasmic fate of the transcript. For instance, in S. cerevisiae the nuclear Pab, Nab2, is not detected in polyribosomes (70) in the cytoplasm, suggesting that information technology most likely is removed and replaced by Pab1, the principle cytoplasmic Pabs important for mRNA stability and translation efficacy (44).
A timeline for the molecular displacements that occur in the course of mRNA consign. In S. cerevisiae, adaptor proteins responsible for the recruitment of mRNA export receptors are deposited upon transcripts (denoted by blackness curved lines to a higher place the large directional arrow) during transcription and processing, coupling these processes to mRNA export. During transcription, components of the THO complex are initially deposited on the nascent transcript. Other processing factors and RNA-bounden proteins, such as Hrp1, Npl3, Sub2, Yra1 and Nab2 are subsequently recruited to the maturing transcript through a combination of interactions with THO components, the C-terminal domain of RNA polymerase II, and other mechanisms. The principle yeast mRNA consign receptor heterodimer, Mex67:Mtr2, is after recruited via interactions with adaptor proteins. Recruitment of Mex67:Mtr2 displaces Sub2 (denoted past blacked curved lines below the large directional arrow), somewhen Yra1 is likewise displaced from the mRNA transcript, and the mRNP exits the nucleus through the nuclear pore complex. Once in the cytoplasm, the Dbp5 helicase remodels the mRNP, displacing export factors, such every bit Mex67 and Nab2, and later on allowing translation factors to bind to the transcript. Equally both Npl3 and Hrp1 associate with polyribosomes, the machinery by which these proteins dissociate from the transcript is unclear (represented by white dashed lines below the large directional arrow). The machinery and compartment of THO displacement also remains unclear, as the hTHO components shuttle between the nucleus and the cytoplasm, but shuttling of S. cerevisiae THO components has non been reported
I component of the machinery in South. cerevisiae responsible for mRNP reorganization upon entry into the cytoplasm is the RNA helicase, Dbp5 (71). Dbp5 (also known as Rat8) is conserved from yeast to higher eukaryotes (71,72) and belongs to the family of DEAD-box RNA helicases, which unwind short stretches of double-stranded RNA or remodel RNA–protein interactions (73). Early work showed that Dbp5 is localized to the cytoplasmic fibrils of the NPC at steady country (72) and is required for proper nuclear export of poly(A) RNA (71), hinting at a part for Dbp5 in the terminal stages of poly(A) RNA consign equally mRNPs exit the NPC. More contempo studies accept corroborated that thought and provided new insight into the role of Dbp5 in poly(A) RNA export. During the final stage of nuclear consign, Dbp5 contacts its activator, the NPC-associated Gle1, as well as the small coactivator molecule, inositol hexakisphosphate (InsP6) (72,74), leading to activation of Dbp5 at the cytoplasmic face of the NPC. Once activated, Dbp5 facilitates the removal of mRNA export factors, including Nab2 and Mex67 (74,75). Whether it is Dbp5 removing proteins from transcripts equally they exit the NPC or other RNA helicases remodeling complexes during the splicing out of introns or other processing events (73), a drove of RNA helicases play critical roles in remodeling mRNP complexes throughout mRNA biogenesis. Hereafter studies investigating the specificity and action of each of these helicases volition provide necessary insight into the mechanisms by which 'molecular wardrobe changes' couple various steps of mRNA biogenesis.
Concluding Remarks
Along the mRNA assembly line from transcription in the nucleus to translation in the cytoplasm, several important unanswered questions remain. Key among these questions is the principle molecular role of many of the proteins involved in mRNA consign. Although numerous proteins have been implicated in mRNA export, these implications are primarily because of the fact that disruption of gene product function results in the nuclear accumulation of poly(A) RNA and not because their role in mRNA export is defined. Many of these proteins may play specific roles during mRNA biogenesis beyond interim as mere adaptors for mRNA export receptors. For example, Yra1, a principle adaptor for Mex67, has RNA-annealing activity (14), and its higher eukaryotic orthologue, Aly/REF, has been constitute associated with the EJC (64), but beyond acting equally an adaptor for Mex67, no precise molecular office of Yra1 in mRNA processing has notwithstanding been described. Future studies investigating the cellular function of Yra1 and other similar RNA-bounden proteins may give critical insight into the mechanisms past which processing events in the mRNA assembly line are coupled with mRNA consign.
Some other question that has nonetheless to be addressed is the mechanism past which the cell distinguishes those transcripts that are competent for consign from those that are not. Several quality control mechanisms be within the cell to degrade faulty transcripts (76). Instead of examining the sequence of the mRNA transcript itself, these quality command systems presumably detect marker proteins deposited upon the transcript following processing. Similar shipping labels on newly manufactured products, these markers would be scanned by the quality control machinery as the transcripts roll off the RNA assembly line. Hereafter studies investigating the identity of these markers will provide insight into nevertheless some other level of mail service-transcriptional regulation of gene expression.
References
1. Moore MJ. From birth to death: the complex lives of eukaryotic mRNAs. Science. 2005;309:1514–1518. [PubMed] [Google Scholar]
ii. Segref A, Sharma K, Doye Five, Hellwig A, Huber J, Luhrmann R, Injure E. Mex67p, a novel gene for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores. EMBO J. 1997;16:3256–3271. [PMC free commodity] [PubMed] [Google Scholar]
3. Katahira J, Strasser Chiliad, Podtelejnikov A, Isle of mann Chiliad, Jung JU, Injure E. The Mex67p-mediated nuclear mRNA consign pathway is conserved from yeast to human. EMBO J. 1999;18:2593–2609. [PMC gratuitous article] [PubMed] [Google Scholar]
4. Kang Y, Bogerd HP, Yang J, Cullen BR. Analysis of the RNA binding specificity of the human tap protein, a constitutive transport element-specific nuclear RNA export cistron. Virology. 1999;262:200–209. [PubMed] [Google Scholar]
v. Strasser Yard, Hurt Eastward. Yra1p, a conserved nuclear RNA-binding protein, interacts straight with Mex67p and is required for mRNA export. EMBO J. 2000;19:410–420. [PMC free commodity] [PubMed] [Google Scholar]
6. Stutz F, Bachi A, Doerks T, Braun IC, Seraphin B, Wilm Chiliad, Bork P, Izaurralde E. REF, an evolutionary conserved family of hnRNP-similar proteins, interacts with TAP/Mex67p and participates in mRNA nuclear consign. RNA. 2000;6:638–650. [PMC costless article] [PubMed] [Google Scholar]
seven. Chavez South, Beilharz T, Rondon AG, Erdjument-Bromage H, Tempst P, Svejstrup JQ, Lithgow T, Aguilera A. A protein circuitous containing Tho2, Hpr1, Mft1 and a novel poly peptide, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. EMBO J. 2000;19:5824–5834. [PMC free article] [PubMed] [Google Scholar]
8. Abruzzi KC, Lacadie Due south, Rosbash One thousand. Biochemical analysis of TREX circuitous recruitment to intronless and intron-containing yeast genes. EMBO J. 2004;23:2620–2631. [PMC complimentary article] [PubMed] [Google Scholar]
ix. Reed R, Cheng H. TREX, SR proteins and export of mRNA. Curr Opin Cell Biol. 2005;17:269–273. [PubMed] [Google Scholar]
10. Strasser Thou, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl One thousand, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002;417:304–308. [PubMed] [Google Scholar]
11. Jensen TH, Patricio M, McCarthy T, Rosbash K. A block to mRNA nuclear consign in S. cerevisiae leads to hyperadenylation of transcripts that accrue at the site of transcription. Mol Jail cell. 2001;seven:887–898. [PubMed] [Google Scholar]
12. Strasser K, Hurt East. Splicing gene Sub2p is required for nuclear mRNA export through its interaction with Yra1p. Nature. 2001;413:648–652. [PubMed] [Google Scholar]
thirteen. Libri D, Graziani North, Saguez C, Boulay J. Multiple roles for the yeast Sub2/yUAP56 cistron in splicing. Genes Dev. 2001;15:36–41. [PMC free article] [PubMed] [Google Scholar]
14. Portman DS, O'Connor JP, Dreyfuss G. Yra1, an essential Saccharomyces cerevisiae gene, encodes a novel nuclear poly peptide with RNA annealing activity. RNA. 1997;3:527–537. [PMC costless article] [PubMed] [Google Scholar]
15. Zenklusen D, Vinciguerra P, Strahm Y, Stutz F. The yeast hnRNP-like proteins Yra1p and Yra2p participate in mRNA export through interaction with Mex67p. Mol Cell Biol. 2001;21:4219–4232. [PMC free article] [PubMed] [Google Scholar]
xvi. Chavez S, Aguilera A. The yeast HPR1 factor has a functional role in transcriptional elongation that uncovers a novel source of genome instability. Genes Dev. 1997;eleven:3459–3470. [PMC free commodity] [PubMed] [Google Scholar]
17. Rondon AG, Jimeno S, Garcia-Rubio G, Aguilera A. Molecular prove that the eukaryotic THO/TREX circuitous is required for efficient transcription elongation. J Biol Chem. 2003;278:39037–39043. [PubMed] [Google Scholar]
18. Zenklusen D, Vinciguerra P, Wyss JC, Stutz F. Stable mRNP formation and export require cotranscriptional recruitment of the mRNA export factors Yra1p and Sub2p by Hpr1p. Mol Cell Biol. 2002;22:8241–8253. [PMC gratis commodity] [PubMed] [Google Scholar]
19. Johnson SA, Cubberley Chiliad, Bentley DL. Cotranscriptional recruitment of the mRNA export cistron Yra1 past direct interaction with the three′ end processing factor Pcf11. Mol Cell. 2009;33:215–226. [PMC complimentary article] [PubMed] [Google Scholar]
20. Gwizdek C, Iglesias Northward, Rodriguez MS, Ossareh-Nazari B, Hobeika M, Divita G, Stutz F, Dargemont C. Ubiquitin-associated domain of Mex67 synchronizes recruitment of the mRNA export machinery with transcription. Proc Natl Acad Sci U S A. 2006;103:16376–16381. [PMC free article] [PubMed] [Google Scholar]
21. Gilbert W, Guthrie C. The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA. Mol Cell. 2004;13:201–212. [PubMed] [Google Scholar]
22. Bucheli ME, Buratowski S. Npl3 is an antagonist of mRNA iii′ stop formation by RNA polymerase Two. EMBO J. 2005;24:2150–2160. [PMC gratuitous article] [PubMed] [Google Scholar]
23. Kress TL, Krogan NJ, Guthrie C. A single SR-like protein, Npl3, promotes pre-mRNA splicing in budding yeast. Mol Cell. 2008;32:727–734. [PMC free article] [PubMed] [Google Scholar]
24. Lee MS, Henry M, Silverish PA. A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export. Genes Dev. 1996;10:1233–1246. [PubMed] [Google Scholar]
25. Bucheli ME, He Ten, Kaplan CD, Moore CL, Buratowski South. Polyadenylation site choice in yeast is affected by competition betwixt Npl3 and polyadenylation factor CFI. RNA. 2007;13:1756–1764. [PMC gratis commodity] [PubMed] [Google Scholar]
26. Barilla D, Lee BA, Proudfoot NJ. Cleavage/polyadenylation factor IA associates with the carboxyl-terminal domain of RNA polymerase II in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2001;98:445–450. [PMC free article] [PubMed] [Google Scholar]
27. Licatalosi DD, Geiger G, Minet M, Schroeder S, Cilli Thousand, McNeil JB, Bentley DL. Functional interaction of yeast pre-mRNA 3′ end processing factors with RNA polymerase II. Mol Prison cell. 2002;9:1101–1111. [PubMed] [Google Scholar]
28. Sadowski M, Dichtl B, Hubner Due west, Keller W. Independent functions of yeast Pcf11p in pre-mRNA 3′ finish processing and in transcription termination. EMBO J. 2003;22:2167–2177. [PMC free article] [PubMed] [Google Scholar]
thirty. Hieronymus H, Silver PA. Genome-wide analysis of RNA-protein interactions illustrates specificity of the mRNA export mechanism. Nat Genet. 2003;33:155–161. [PubMed] [Google Scholar]
31. Guisbert KK, Duncan K, Li H, Guthrie C. Functional specificity of shuttling hnRNPs revealed by genome-wide analysis of their RNA bounden profiles. RNA. 2005;11:383–393. [PMC free article] [PubMed] [Google Scholar]
32. Proudfoot Due north, O'Sullivan J. Polyadenylation: a tail of ii complexes. Curr Biol. 2002;12:R855–R857. [PubMed] [Google Scholar]
33. Coller JM, Gray NK, Wickens MP. mRNA stabilization by poly(A) binding protein is independent of poly(A) and requires translation. Genes Dev. 1998;12:3226–3235. [PMC free article] [PubMed] [Google Scholar]
34. Hammell CM, Gross Southward, Zenklusen D, Heath CV, Stutz F, Moore C, Cole CN. Coupling of termination, 3′ processing, and mRNA export. Mol Prison cell Biol. 2002;22:6441–6457. [PMC free article] [PubMed] [Google Scholar]
35. Brodsky Equally, Argent PA. Pre-mRNA processing factors are required for nuclear export. RNA. 2000;6:1737–1749. [PMC free article] [PubMed] [Google Scholar]
36. Libri D, Dower Chiliad, Boulay J, Thomsen R, Rosbash M, Jensen Th. Interactions between mRNA export commitment, 3′-end quality control, and nuclear degradation. Mol Cell Biol. 2002;22:8254–8266. [PMC gratuitous article] [PubMed] [Google Scholar]
37. Hilleren P, Parker R. Defects in the mRNA export factors Rat7p, Gle1p, Mex67p, and Rat8p crusade hyperadenylation during 3′-end formation of nascent transcripts. RNA. 2001;7:753–764. [PMC complimentary commodity] [PubMed] [Google Scholar]
38. Saguez C, Olesen JR, Jensen Th. Formation of export-competent mRNP: escaping nuclear devastation. Curr Opin Cell Biol. 2005;17:287–293. [PubMed] [Google Scholar]
39. Iglesias Due north, Stutz F. Regulation of mRNP dynamics along the export pathway. FEBS Lett. 2008;582:1987–1996. [PubMed] [Google Scholar]
40. Dower K, Kuperwasser N, Merrikh H, Rosbash M. A synthetic A tail rescues yeast nuclear accumulation of a ribozyme-terminated transcript. RNA. 2004;10:1888–1899. [PMC gratuitous article] [PubMed] [Google Scholar]
41. Abruzzi KC, Belostotsky DA, Chekanova JA, Dower K, Rosbash K. 3′-end germination signals modulate the clan of genes with the nuclear periphery equally well equally mRNP dot germination. EMBO J. 2006;25:4253–4262. [PMC free article] [PubMed] [Google Scholar]
42. Symons RH. Small-scale catalytic RNAs. Annu Rev Biochem. 1992;61:641–671. [PubMed] [Google Scholar]
43. Duvel K, Valerius O, Mangus DA, Jacobson A, Braus GH. Replacement of the yeast TRP4 iii′ untranslated region by a hammerhead ribozyme results in a stable and efficiently exported mRNA that lacks a poly(A) tail. RNA. 2002;8:336–344. [PMC costless article] [PubMed] [Google Scholar]
44. Mangus DA, Evans MC, Jacobson A. Poly(A)-binding proteins: multifunctional scaffolds for the mail-transcriptional control of gene expression. Genome Biol. 2003;four:223. [PMC free article] [PubMed] [Google Scholar]
45. Dunn EF, Hammell CM, Hodge CA, Cole CN. Yeast poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis to export. Genes Dev. 2005;xix:xc–103. [PMC free article] [PubMed] [Google Scholar]
46. Brune C, Munchel SE, Fischer Due north, Podtelejnikov AV, Weis M. Yeast poly(A)-bounden protein Pab1 shuttles between the nucleus and the cytoplasm and functions in mRNA export. RNA. 2005;xi:517–531. [PMC free article] [PubMed] [Google Scholar]
47. Amrani North, Minet M, Le Gouar M, Lacroute F, Wyers F. Yeast Pab1 interacts with Rna15 and participates in the control of the poly(A) tail length in vitro. Mol Cell Biol. 1997;17:3694–3701. [PMC free article] [PubMed] [Google Scholar]
48. Minvielle-Sebastia L, Preker PJ, Wiederkehr T, Strahm Y, Keller Due west. The major yeast poly(A)-binding protein is associated with cleavage factor IA and functions in premessenger RNA 3′-end formation. Proc Natl Acad Sci U South A. 1997;94:7897–7902. [PMC gratis article] [PubMed] [Google Scholar]
49. Kelly SM, Pabit SA, Kitchen CM, Guo P, Marfatia KA, Murphy TJ, Corbett AH, Berland KM. Recognition of polyadenosine RNA by zinc finger proteins. Proc Natl Acad Sci U S A. 2007;104:12306–12311. [PMC costless article] [PubMed] [Google Scholar]
50. Perreault A, Lemieux C, Bachand F. Regulation of the nuclear poly(A)-binding protein by arginine methylation in fission yeast. J Biol Chem. 2007;282:7552–7562. [PubMed] [Google Scholar]
51. Kerwitz Y, Kuhn U, Lilie H, Knoth A, Scheuermann T, Friedrich H, Schwarz Due east, Wahle Due east. Stimulation of poly(A) polymerase through a direct interaction with the nuclear poly(A) binding protein allosterically regulated by RNA. EMBO J. 2003;22:3705–3714. [PMC gratis article] [PubMed] [Google Scholar]
52. Anderson JT, Wilson SM, Datar KV, Swanson MS. NAB2: a yeast nuclear polyadenylated RNA-binding poly peptide essential for cell viability. Mol Cell Biol. 1993;13:2730–2741. [PMC complimentary commodity] [PubMed] [Google Scholar]
53. Hector RE, Nykamp KR, Dheur Due south, Anderson JT, Not PJ, Urbinati CR, Wilson SM, Minvielle-Sebastia 50, Swanson MS. Dual requirement for yeast hnRNP Nab2p in mRNA poly(A) tail length command and nuclear export. EMBO J. 2002;21:1800–1810. [PMC free commodity] [PubMed] [Google Scholar]
54. Viphakone N, Voisinet-Hakil F, Minvielle-Sebastia L. Molecular autopsy of mRNA poly(A) tail length control in yeast. Nucleic Acids Res. 2008;36:2418–2433. [PMC free article] [PubMed] [Google Scholar]
55. Marfatia KA, Crafton EB, Dark-green DM, Corbett AH. Domain analysis of the Saccharomyces cerevisiae heterogeneous nuclear ribonucleoprotein, Nab2p. Dissecting the requirements for Nab2p-facilitated poly(A) RNA consign. J Biol Chem. 2003;278:6731–6740. [PubMed] [Google Scholar]
56. Fasken MB, Stewart M, Corbett AH. Functional significance of the interaction between the mRNA-binding poly peptide, Nab2, and the nuclear pore-associated protein, Mlp1, in mRNA export. J Biol Chem. 2008;283:27130–27143. [PMC free article] [PubMed] [Google Scholar]
57. Vinciguerra P, Iglesias N, Camblong J, Zenklusen D, Stutz F. Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export. EMBO J. 2005;24:813–823. [PMC complimentary article] [PubMed] [Google Scholar]
58. Masuda Due south, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005;19:1512–1517. [PMC gratuitous article] [PubMed] [Google Scholar]
59. Kohler A, Injure E. Exporting RNA from the nucleus to the cytoplasm. Nat Rev Mol Prison cell Biol. 2007;8:761–773. [PubMed] [Google Scholar]
threescore. Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human being mRNA export machinery recruited to the 5′ end of mRNA. Jail cell. 2006;127:1389–1400. [PubMed] [Google Scholar]
61. Zhou Z, Luo MJ, Straesser K, Katahira J, Injure Eastward, Reed R. The protein Aly links pre-messenger-RNA splicing to nuclear export in metazoans. Nature. 2000;407:401–405. [PubMed] [Google Scholar]
62. Jurica MS, Moore MJ. Pre-mRNA splicing: awash in a ocean of proteins. Mol Cell. 2003;12:5–14. [PubMed] [Google Scholar]
63. Fleckner J, Zhang Chiliad, Valcarcel J, Green MR. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997;11:1864–1872. [PubMed] [Google Scholar]
64. Le Hir H, Izaurralde East, Maquat LE, Moore MJ. The spliceosome deposits multiple proteins xx–24 nucleotides upstream of mRNA exon-exon junctions. EMBO J. 2000;nineteen:6860–6869. [PMC free commodity] [PubMed] [Google Scholar]
65. Katahira J, Inoue H, Injure East, Yoneda Y. Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J. 2009;28(5):556–567. [PMC free article] [PubMed] [Google Scholar]
66. Nojima T, Hirose T, Kimura H, Hagiwara M. The interaction between cap-binding circuitous and RNA export factor is required for intronless mRNA export. J Biol Chem. 2007;282:15645–15651. [PubMed] [Google Scholar]
67. Terry LJ, Wente SR. Nuclear mRNA export requires specific FG nucleoporins for translocation through the nuclear pore complex. J Jail cell Biol. 2007;178:1121–1132. [PMC free article] [PubMed] [Google Scholar]
68. Weis One thousand. The nuclear pore complex: oily spaghetti or viscid behave? Prison cell. 2007;130:405–407. [PubMed] [Google Scholar]
69. Strawn LA, Shen T, Wente SR. The GLFG regions of Nup116p and Nup100p serve every bit binding sites for both Kap95p and Mex67p at the nuclear pore circuitous. J Biol Chem. 2001;276:6445–6452. [PubMed] [Google Scholar]
lxx. Windgassen M, Sturm D, Cajigas IJ, Gonzalez CI, Seedorf M, Bastians H, Krebber H. Yeast shuttling SR proteins Npl3p, Gbp2p, and Hrb1p are role of the translating mRNPs, and Npl3p can role as a translational repressor. Mol Cell Biol. 2004;24:10479–10491. [PMC costless article] [PubMed] [Google Scholar]
71. Snay-Hodge CA, Colot HV, Goldstein AL, Cole CN. Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box poly peptide essential for RNA export. EMBO J. 1998;17:2663–2676. [PMC complimentary article] [PubMed] [Google Scholar]
72. Schmitt C, Von Kobbe C, Bachi A, Pante North, Rodrigues JP, Boscheron C, Rigaut Thou, Wilm M, Seraphin B, Carmo-Fonseca Grand, Izaurralde Eastward. Dbp5, a DEAD-box poly peptide required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with Tin can/Nup159p. EMBO J. 1999;18:4332–4347. [PMC free article] [PubMed] [Google Scholar]
73. Tanner NK, Linder P. DExD/H box RNA helicases: from generic motors to specific dissociation functions. Mol Jail cell. 2001;eight:251–262. [PubMed] [Google Scholar]
74. Tran EJ, Zhou Y, Corbett AH, Wente SR. The Dead-box protein Dbp5 controls mRNA export past triggering specific RNA:protein remodeling events. Mol Cell. 2007;28:850–859. [PubMed] [Google Scholar]
75. Lund MK, Guthrie C. The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim. Mol Cell. 2005;20:645–651. [PubMed] [Google Scholar]
76. Fasken MB, Corbett AH. Process or perish: quality command in mRNA biogenesis. Nat Struct Mol Biol. 2005;12:482–488. [PubMed] [Google Scholar]
77. Rougemaille One thousand, Gudipati RK, Olesen JR, Thomsen R, Seraphin B, Libri D, Jensen TH. Dissecting mechanisms of nuclear mRNA surveillance in THO/Sub2 complex mutants. EMBO J. 2007;26:2317–2326. [PMC free article] [PubMed] [Google Scholar]
78. Fischer T, Strasser K, Racz A, Rodriguez-Navarro S, Oppizzi M, Ihrig P, Lechner J, Hurt Eastward. The mRNA export machinery requires the novel Sac3p-Thp1p complex to dock at the nucleoplasmic entrance of the nuclear pores. EMBO J. 2002;21:5843–5852. [PMC gratuitous article] [PubMed] [Google Scholar]
79. Katahira J, Yoneda Y. Roles of the TREX complex in nuclear consign of mRNA. RNA Biol. 2009;6:149–152. [PubMed] [Google Scholar]
lxxx. Mancini A, El Bounkari O, Norrenbrock AF, Scherr Grand, Schaefer D, Eder M, Banham AH, Pulford Grand, Lyne L, Whetton Advertisement, Tamura T. FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBP alpha. Oncogene. 2007;26:1020–1027. [PubMed] [Google Scholar]
81. Shen H. UAP56-a primal player with surprisingly diverse roles in pre-mRNA splicing and nuclear export. BMB Rep. 2009;42:185–188. [PubMed] [Google Scholar]
82. Yao W, Roser D, Kohler A, Bradatsch B, Bassler J, Hurt E. Nuclear consign of ribosomal 60S subunits past the general mRNA export receptor Mex67-Mtr2. Mol Cell. 2007;26:51–62. [PubMed] [Google Scholar]
83. Hurt Eastward, Strasser Thou, Segref A, Bailer South, Schlaich N, Presutti C, Tollervey D, Jansen R. Mex67p mediates nuclear export of a variety of RNA polymerase II transcripts. J Biol Chem. 2000;275:8361–8368. [PubMed] [Google Scholar]
84. Gross S, Moore C. Five subunits are required for reconstitution of the cleavage and polyadenylation activities of Saccharomyces cerevisiae cleavage factor I. Proc Natl Acad Sci U Southward A. 2001;98:6080–6085. [PMC gratuitous article] [PubMed] [Google Scholar]
85. Proudfoot N. New perspectives on connecting messenger RNA 3′ end formation to transcription. Curr Opin Prison cell Biol. 2004;sixteen:272–278. [PubMed] [Google Scholar]
86. Leung SW, Apponi LH, Cornejo OE, Kitchen CM, Valentini SR, Pavlath GK, Dunham CM, Corbett AH. Splice variants of the human ZC3H14 gene generate multiple isoforms of a zinc finger polyadenosine RNA bounden protein. Factor. 2009;439(one–two):71–78. [PMC complimentary commodity] [PubMed] [Google Scholar]
87. Scarcelli JJ, Viggiano S, Hodge CA, Heath CV, Amberg DC, Cole CN. Constructed genetic array analysis in Saccharomyces cerevisiae provides evidence for an interaction between RAT8/DBP5 and genes encoding P-trunk components. Genetics. 2008;179:1945–1955. [PMC free article] [PubMed] [Google Scholar]
88. Bolger TA, Folkmann AW, Tran EJ, Wente SR. The mRNA export gene Gle1 and inositol hexakisphosphate regulate distinct stages of translation. Prison cell. 2008;134:624–633. [PMC free article] [PubMed] [Google Scholar]
89. Weirich CS, Erzberger JP, Flick JS, Berger JM, Thorner J, Weis K. Activation of the DExD/H-box protein Dbp5 by the nuclear-pore protein Gle1 and its coactivator InsP6 is required for mRNA export. Nat Prison cell Biol. 2006;8:668–676. [PubMed] [Google Scholar]
90. Alcazar-Roman AR, Tran EJ, Guo Due south, Wente SR. Inositol hexakisphosphate and Gle1 activate the DEAD-box protein Dbp5 for nuclear mRNA consign. Nat Cell Biol. 2006;8:711–716. [PubMed] [Google Scholar]
91. Irish potato R, Wente SR. An RNA-export mediator with an essential nuclear consign signal. Nature. 1996;383:357–360. [PubMed] [Google Scholar]
92. Watkins JL, Murphy R, Emtage JL, Wente SR. The human being homologue of Saccharomyces cerevisiae Gle1p is required for poly(A)+ RNA export. Proc Natl Acad Sci U South A. 1998;95:6779–6784. [PMC gratis commodity] [PubMed] [Google Scholar]
93. Saavedra CA, Hammell CM, Heath CV, Cole CN. Yeast heat daze mRNAs are exported through a distinct pathway divers by Rip1p. Genes Dev. 1997;xi:2845–2856. [PMC free commodity] [PubMed] [Google Scholar]
94. Gallardo M, Aguilera A. A new hyperrecombination mutation identifies a novel yeast gene, THP1, connecting transcription elongation with mitotic recombination. Genetics. 2001;157:79–89. [PMC gratuitous commodity] [PubMed] [Google Scholar]
95. Gonzalez-Aguilera C, Tous C, Gomez-Gonzalez B, Huertas P, Luna R, Aguilera A. The THP1-SAC3-SUS1-CDC31 circuitous works in transcription elongation-mRNA consign preventing RNA-mediated genome instability. Mol Biol Jail cell. 2008;19:4310–4318. [PMC gratuitous article] [PubMed] [Google Scholar]
96. Luna R, Gonzalez-Aguilera C, Aguilera A. Transcription at the proximity of the nuclear pore: a role for the THP1-SAC3-SUS1-CDC31 (THSC) circuitous. RNA Biol. 2009;6:145–148. [PubMed] [Google Scholar]
97. Thomsen R, Saguez C, Nasser T, Jensen Thursday. General, rapid, and transcription-dependent fragmentation of nucleolar antigens in S. cerevisiae mRNA consign mutants. RNA. 2008;14:706–716. [PMC free article] [PubMed] [Google Scholar]
98. Jani D, Lutz S, Marshall NJ, Fischer T, Kohler A, Ellisdon AM, Hurt Eastward, Stewart M. Sus1, Cdc31, and the Sac3 CID region form a conserved interaction platform that promotes nuclear pore association and mRNA consign. Mol Jail cell. 2009;33:727–737. [PMC free article] [PubMed] [Google Scholar]
99. Pascual-Garcia P, Rodriguez-Navarro South. A tale of coupling, Sus1 function in transcription and mRNA export. RNA Biol. 2009;6:141–144. [PubMed] [Google Scholar]
100. Rodriguez-Navarro S, Fischer T, Luo MJ, Antunez O, Brettschneider S, Lechner J, Perez-Ortin JE, Reed R, Hurt Eastward. Sus1, a functional component of the SAGA histone acetylase complex and the nuclear pore-associated mRNA export machinery. Cell. 2004;116:75–86. [PubMed] [Google Scholar]
101. Helfant AH. Composition of the spindle pole body of Saccharomyces cerevisiae and the proteins involved in its duplication. Curr Genet. 2002;40:291–310. [PubMed] [Google Scholar]
102. Fischer T, Rodriguez-Navarro S, Pereira K, Racz A, Schiebel East, Hurt E. Yeast centrin Cdc31 is linked to the nuclear mRNA consign mechanism. Nat Cell Biol. 2004;6:840–848. [PubMed] [Google Scholar]
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702165/
0 Response to "What Happens to the Transcript Rna Before It Leaves the Nucleus"
Post a Comment