Functional coupling of transcription and splicing

Montes, Marta; Becerra, Soraya; Sánchez-Álvarez, Miguel; Suñé, Carlos

doi:10.1016/j.gene.2012.04.006

Cited by 58 publications

(47 citation statements)

References 217 publications

(258 reference statements)

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“…Since the first significant observation of co-transcriptional spliceosome assembly from electron micrographs of Drosophila melanogaster embryonic transcription units (37), increasing evidence supports the idea that transcription and splicing are physically and functionally coupled, and has also uncovered the intricate association between mRNA splicing, RNA polymerase II (Pol II) and chromatin structure (38,39).…”

Section: Coupling Of Alternative Splicing To Transcriptionmentioning

confidence: 99%

Mechanism of alternative splicing and its regulation

et al. 2014

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Abstract. Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development. Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing. Additional molecular features, such as chromatin structure, RNA structure and alternative transcription initiation or alternative transcription termination, collaborate with these basic components to generate the protein diversity due to alternative splicing.

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Section: Coupling Of Alternative Splicing To Transcriptionmentioning

confidence: 99%

Mechanism of alternative splicing and its regulation

et al. 2014

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“…A number of these regulators are also likely involved in the coupling of alternative splicing to transcription and other RNA processing events (for review, see Moore and Proudfoot 2009;Montes et al 2012).…”

Section: Prpf40b Affects Alternative Splicingmentioning

confidence: 99%

Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF⁶⁵and modulates alternative pre-mRNA splicing in vivo

Becerra¹,

Montes²,

Hernández-Munaín

et al. 2015

RNA

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The first stable complex formed during the assembly of spliceosomes onto pre-mRNA substrates in mammals includes U1 snRNP, which recognizes the 5 ′ splice site, and the splicing factors SF1 and U2AF, which bind the branch point sequence, polypyrimidine tract, and 3 ′ splice site. The 5 ′ and 3 ′ splice site complexes are thought to be joined together by proteinprotein interactions mediated by factors that ensure the fidelity of the initial splice site recognition. In this study, we identified and characterized PRPF40B, a putative mammalian ortholog of the U1 snRNP-associated yeast splicing factor Prp40. PRPF40B is highly enriched in speckles with a behavior similar to splicing factors. We demonstrated that PRPF40B interacts directly with SF1 and associates with U2AF 65 . Accordingly, PRPF40B colocalizes with these splicing factors in the cell nucleus. Splicing assays with reporter minigenes revealed that PRPF40B modulates alternative splice site selection. In the case of Fas regulation of alternative splicing, weak 5 ′ and 3 ′ splice sites and exonic sequences are required for PRPF40B function. Placing our data in a functional context, we also show that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival.

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“…In addition, early mass analysis combined with a novel and precise computational approach provided the first evidence of a putative global role of TCERG1 in mRNA processing (Pearson et al 2008). Given these data, TCERG1 has been suggested as a possible factor that coordinates transcription and splicing (Montes et al 2012a), a hypothesis that we recently supported by demonstrating that TCERG1 regulates alternative splicing of the Bcl-x gene by modulating the rate of RNAPII transcription (Montes et al 2012b).…”

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confidence: 90%

The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing

Sánchez-Hernández

Boireau

Schmidt

et al. 2016

RNA

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Coupling between transcription and RNA processing is key for gene regulation. Using live-cell photobleaching techniques, we investigated the factor TCERG1, which coordinates transcriptional elongation with splicing. We demonstrate that TCERG1 is highly mobile in the nucleoplasm and that this mobility is slightly decreased when it is associated with speckles. Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) but not α-amanitin treatment reduced the mobility of TCERG1, which suggests interaction with paused transcription elongation complexes. We found that TCERG1 mobility is rapid at the transcription site (TS) of a reporter that splices post-transcriptionally and that TCERG1 is recruited to the active TS independent of the CTD of RNAPII, thus excluding phosphorylated CTD as a requirement for recruiting this factor to the TS. Importantly, the mobility of TCERG1 is reduced when the reporter splices cotranscriptionally, which suggests that TCERG1 forms new macromolecular complexes when splicing occurs cotranscriptionally. In this condition, spliceostatin A has no effect, indicating that TCERG1 rapidly binds and dissociates from stalled spliceosomal complexes and that the mobility properties of TCERG1 do not depend on events occurring after the initial spliceosome formation. Taken together, these data suggest that TCERG1 binds independently to elongation and splicing complexes, thus performing their coupling by transient interactions rather than by stable association with one or the other complexes. This finding has conceptual implications for understanding the coupling between transcription and RNA processing.

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Functional coupling of transcription and splicing

Cited by 58 publications

References 217 publications

Mechanism of alternative splicing and its regulation

Mechanism of alternative splicing and its regulation

Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF⁶⁵and modulates alternative pre-mRNA splicing in vivo

The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing

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Functional coupling of transcription and splicing

Cited by 58 publications

References 217 publications

Mechanism of alternative splicing and its regulation

Mechanism of alternative splicing and its regulation

Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF65and modulates alternative pre-mRNA splicing in vivo

The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing

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Prp40 pre-mRNA processing factor 40 homolog B (PRPF40B) associates with SF1 and U2AF⁶⁵and modulates alternative pre-mRNA splicing in vivo