The carboxyl terminus of vertebrate poly(A) polymerase interacts with U2AF 65 to couple 3′-end processing and splicing

Vagner, Stéphan; Vagner, Christine; Mattaj, Iain W.

doi:10.1101/gad.14.4.403

Cited by 141 publications

(26 citation statements)

References 64 publications

(108 reference statements)

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“…In addition to its crucial role in splicing, we have demonstrated that U2AF 65 bound to the polypyrimidine tract of the second and last intron of β‐globin pre‐mRNA promotes 3′ end processing (Millevoi et al , 2002). We have also previously demonstrated that U2AF 65 interacts with PAP (Vagner et al , 2000). Through this interaction, PAP is able to recruit U2AF 65 to an adjacent upstream 3′ splice site, thereby stimulating splicing (Vagner et al , 2000).…”

Section: Introductionmentioning

confidence: 66%

An interaction between U2AF 65 and CF Im links the splicing and 3′ end processing machineries

Millevoi

Loulergue

Dettwiler

et al. 2006

EMBO J

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182

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The protein factor U2 snRNP Auxiliary Factor (U2AF) 65 is an essential component required for splicing and involved in the coupling of splicing and 3 0 end processing of vertebrate pre-mRNAs. Here we have addressed the mechanisms by which U2AF 65 stimulates pre-mRNA 3 0 end processing. We identify an arginine/serine-rich region of U2AF 65 that mediates an interaction with an RS-like alternating charge domain of the 59 kDa subunit of the human cleavage factor I (CF I m ), an essential 3 0 processing factor that functions at an early step in the recognition of the 3 0 end processing signal. Tethered functional analysis shows that the U2AF 65/CF I m 59 interaction stimulates in vitro 3 0 end cleavage and polyadenylation. These results therefore uncover a direct role of the U2AF 65/CF I m 59 interaction in the functional coordination of splicing and 3 0 end processing.

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Section: Introductionmentioning

confidence: 66%

An interaction between U2AF 65 and CF Im links the splicing and 3′ end processing machineries

Millevoi

Loulergue

Dettwiler

et al. 2006

EMBO J

Self Cite

182

178

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show abstract

“…RNase protection assays demonstrated that the UTE assists recognition of the weak cleavage-polyadenylation site, thereby coupling splicing with cleavage and polyadenylation. Interactions of splicing factors with cleavage and polyadenylation factors have been described, for example between U2AF65 and the carboxy terminal region of the poly(A) polymerase (Vagner et al 2000), cleavage and polyadenylation specificity factor (CPSF) (Kyburz et al 2006), or cleavage factor I CF1(m) (Millevoi et al 2006). The UTE is in close vicinity to the branch point, which binds the U2 snRNP.…”

Section: Discussionmentioning

confidence: 99%

Exonization by the Emergence of a Cleavage-Polyadenylation Site

Méreau

Lerivray

Viet

et al. 2022

Preprint

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Exonization is the evolutionary process of recruitment of new exonic regions from previously intronic regions. It is a major contributor to the increased complexity of alternative splicing. Here, we explore exonization mediated by the emergence of a novel cleavage-polyadenylation site in an intron. In Xenopus laevis, the tpm1 gene, which encodes muscular tropomyosin, contains alternative terminal exons. In adult muscles and embryonic hearts, exon 9A is joined to the terminal exon 9B. In embryonic somites, it is joined to the exonic region 9', which is transcribed from the intron immediately downstream of exon 9A. Consequently, exon 9A is either an internal exon when ligated to exon 9B, or a part of a terminal exon along with region 9'. We show here that region 9' is present only in amphibians and coelacanths. This suggests that it emerged in sarcopterygians and was lost in amniotes. We used antisense morpholino oligonucleotides to mask the regions of tpm1 pre-mRNA that potentially regulate the inclusion of exon 9A9'. This revealed that the definition of exon 9A9' relies on a weak cleavage-polyadenylation site and an intronic enhancer, but is independent of the 3' splice site. We demonstrate that RNAs containing exon 9B are toxic in somites. This may have contributed to the evolutionary pressure that led to the exonization of region 9' in sarcopterygians. These findings reveal the emergence of a novel cleavage-polyadenylation site that avoids the accumulation of a toxic RNA as a novel mechanism for exonization-mediated diversification of terminal exons.

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“…For example, mutation of the 3′SS causes a transcription termination defect due to failure to recognize the poly(A) site (Dye & Proudfoot, 1999 ). Interactions between splicing factors, such as SF3B1 or U2AF65, and CPA factors, such as CPSF100 or poly(A) polymerase, PAPOLA, have been demonstrated (Niwa et al , 1990 ; Gunderson et al , 1994 ; Vagner et al , 2000 ; Kyburz et al , 2006 ; Tellier et al , 2020a ). In addition, subunit CDC73 of the PAF complex, which plays a role in elongation, interacts with the CPSF73 CPA endonuclease (Rozenblatt‐Rosen et al , 2009 ).…”

Section: Introductionmentioning

confidence: 99%

CDK9 and PP2A regulate RNA polymerase II transcription termination and coupled RNA maturation

et al. 2022

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CDK9 is a kinase critical for the productive transcription of protein‐coding genes by RNA polymerase II (pol II). As part of P‐TEFb, CDK9 phosphorylates the carboxyl‐terminal domain (CTD) of pol II and elongation factors, which allows pol II to elongate past the early elongation checkpoint (EEC) encountered soon after initiation. We show that, in addition to halting pol II at the EEC, loss of CDK9 activity causes premature termination of transcription across the last exon, loss of polyadenylation factors from chromatin, and loss of polyadenylation of nascent transcripts. Inhibition of the phosphatase PP2A abrogates the premature termination and loss of polyadenylation caused by CDK9 inhibition, indicating that this kinase/phosphatase pair regulates transcription elongation and RNA processing at the end of protein‐coding genes. We also confirm the splicing factor SF3B1 as a target of CDK9 and show that SF3B1 in complex with polyadenylation factors is lost from chromatin after CDK9 inhibition. These results emphasize the important roles that CDK9 plays in coupling transcription elongation and termination to RNA maturation downstream of the EEC.

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The carboxyl terminus of vertebrate poly(A) polymerase interacts with U2AF 65 to couple 3′-end processing and splicing

Cited by 141 publications

References 64 publications

An interaction between U2AF 65 and CF Im links the splicing and 3′ end processing machineries

An interaction between U2AF 65 and CF Im links the splicing and 3′ end processing machineries

Exonization by the Emergence of a Cleavage-Polyadenylation Site

CDK9 and PP2A regulate RNA polymerase II transcription termination and coupled RNA maturation

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