title: mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription.
abstract: We report a function of human mRNA decapping factors in control of transcription by RNA polymerase II. Decapping proteins Edc3, Dcp1a, and Dcp2 and the termination factor TTF2 coimmunoprecipitate with Xrn2, the nuclear 5'-3' exonuclease "torpedo" that facilitates transcription termination at the 3' ends of genes. Dcp1a, Xrn2, and TTF2 localize near transcription start sites (TSSs) by ChIP-seq. At genes with 5' peaks of paused pol II, knockdown of decapping or termination factors Xrn2 and TTF2 shifted polymerase away from the TSS toward upstream and downstream distal positions. This redistribution of pol II is similar in magnitude to that caused by depletion of the elongation factor Spt5. We propose that coupled decapping of nascent transcripts and premature termination by the "torpedo" mechanism is a widespread mechanism that limits bidirectional pol II elongation. Regulated cotranscriptional decapping near promoter-proximal pause sites followed by premature termination could control productive pol II elongation.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Brannan
authors.forename: Hyunmin
authors.initials: H
authors.lastname: Kim
authors.forename: Benjamin
authors.initials: B
authors.lastname: Erickson
authors.forename: Kira
authors.initials: K
authors.lastname: Glover-Cutter
authors.forename: Soojin
authors.initials: S
authors.lastname: Kim
authors.forename: Nova
authors.initials: N
authors.lastname: Fong
authors.forename: Lauren
authors.initials: L
authors.lastname: Kiemele
authors.forename: Kirk
authors.initials: K
authors.lastname: Hansen
authors.forename: Richard
authors.initials: R
authors.lastname: Davis
authors.forename: Jens
authors.initials: J
authors.lastname: Lykke-Andersen
authors.forename: David L
authors.initials: DL
authors.lastname: Bentley
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D005095:Exoribonucleases / Q000502:physiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D025941:Protein Interaction Mapping; D012319:RNA Polymerase II / Q000502:physiology*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D012319:RNA Polymerase II; D005095:Exoribonucleases; C120903:XRN2 protein, human; D000251:Adenosine Triphosphatases; C477874:TTF2 protein, human