Journal
CELL
Volume 150, Issue 6, Pages 1147-1157Publisher
CELL PRESS
DOI: 10.1016/j.cell.2012.08.004
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Funding
- ERC [250333]
- ANR-BLAN [0040]
- Sidaction
- ANRS
- FRM equipe labellisee''
- ANR
- ERC
- CNRS
- FRM
- RTRS grand Sud
- The Netherlands Organization for Scientific Research (NWO-CW)
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Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 30-50 exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation.
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