Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII

Cell. 2012 Sep 14;150(6):1147-57. doi: 10.1016/j.cell.2012.08.004.


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 3'-5' 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • DNA Helicases
  • Exoribonucleases / metabolism*
  • Exosome Multienzyme Ribonuclease Complex / metabolism*
  • Gene Expression Regulation, Viral*
  • HIV Long Terminal Repeat
  • HIV-1 / genetics*
  • Humans
  • Molecular Sequence Data
  • Multifunctional Enzymes
  • Promoter Regions, Genetic
  • RNA Helicases / metabolism*
  • RNA Interference
  • RNA Polymerase II / metabolism*
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*


  • Multifunctional Enzymes
  • RNA, Viral
  • Transcription Factors
  • RNA Polymerase II
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • EXOSC10 protein, human
  • XRN2 protein, human
  • SETX protein, human
  • DNA Helicases
  • RNA Helicases