The multifunctional Ccr4-Not complex directly promotes transcription elongation

Jennifer A. Kruk, Arnob Dutta, Jianhua Fu, David S. Gilmour, Joseph C. Reese

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

The Ccr4-Not complex has been implicated in the control of multiple steps of mRNA metabolism; however, its functions in transcription remain ambiguous. The discovery that Ccr4/Pop2 is the major cytoplasmic mRNA deadenylase and the detection of Not proteins within mRNA processing bodies have raised questions about the roles of the Ccr4-Not complex in transcription. Here we firmly establish Ccr4-Not as a positive elongation factor for RNA polymerase II (RNAPII). The Ccr4-Not complex is targeted to the coding region of genes in a transcription-dependent manner similar to RNAPII and promotes elongation in vivo. Furthermore, Ccr4-Not interacts directly with elongating RNAPII complexes and stimulates transcription elongation of arrested polymerase in vitro. Ccr4-Not can reactivate backtracked RNAPII using a mechanism different from that of the well-characterized elongation factor TFIIS. While not essential for its interaction with elongation complexes, Ccr4-Not interacts with the emerging transcript and promotes elongation in a manner dependent on transcript length, although this interaction is not required for it to bind RNAPII. Our comprehensive analysis shows that Ccr4-Not directly regulates transcription, and suggests it does so by promoting the resumption of elongation of arrested RNAPII when it encounters transcriptional blocks in vivo.

Original languageEnglish (US)
Pages (from-to)581-593
Number of pages13
JournalGenes and Development
Volume25
Issue number6
DOIs
StatePublished - Mar 15 2011

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All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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