Coordination of RNA polymerase II pausing and 3' end processing factor recruitment with alternative polyadenylation

Becky Fusby, Soojin Kim, Benjamin Erickson, Hyunmin Kim, Martha L. Peterson, David L. Bentley

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2 residues of its heptad repeats (YS2PTSPS). The function of cotranscriptional events in the selection of alternative poly(A) sites is poorly understood. We investigated Pol II pausing, CTD Ser2 phosphorylation, and processing factor CstF recruitment at wild-type and mutant IgM transgenes that use alternative poly(A) sites to produce mRNAs encoding the secreted and membrane-bound forms of the immunoglobulin (Ig) heavy chain. The results show that the sites of Pol II pausing and processing factor recruitment change depending on which poly(A) site is utilized. In contrast, the extent of Pol II CTD Ser2 phosphorylation does not closely correlate with poly(A) site selection. We conclude that changes in properties of the transcription elongation complex closely correlate with utilization of different poly(A) sites, suggesting that cotranscriptional events may influence the decision between alternative modes of pre-mRNA 3' end processing.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalMolecular and Cellular Biology
Volume36
Issue number2
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
HHS | NIH | National Institute of General Medical Sciences (NIGMS) provided funding to David Bentley under grant number GM58613. NSF | BIO | Division of Molecular and Cellular Biosciences (MCB) provided funding to Martha L. Peterson under grant number MCB-0919099.

Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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