mRNA Decapping Factors and the Exonuclease Xrn2 Function in Widespread Premature Termination of RNA Polymerase II Transcription

被引:165
作者
Brannan, Kris [1 ]
Kim, Hyunmin [1 ]
Erickson, Benjamin [1 ]
Glover-Cutter, Kira [1 ]
Kim, Soojin [1 ]
Fong, Nova [1 ]
Kiemele, Lauren [1 ]
Hansen, Kirk [1 ]
Davis, Richard [1 ]
Lykke-Andersen, Jens [2 ]
Bentley, David L. [1 ]
机构
[1] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Aurora, CO 80045 USA
[2] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA
关键词
BINDING-PROTEIN; C-MYC; NUCLEOSOMAL TEMPLATES; ANTI-TERMINATION; MAMMALIAN-CELLS; HUMAN PROMOTERS; MEDIATED DECAY; YEAST; ELONGATION; ENZYMES;
D O I
10.1016/j.molcel.2012.03.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:311 / 324
页数:14
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