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Ccr4‐Not complex directly regulates transcription elongation
Author(s) -
Reese Joseph C,
Kruk Jennifer A.,
Dutta Arnob,
Gilmour David S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.186.2
Subject(s) - transcription preinitiation complex , transcription (linguistics) , microbiology and biotechnology , rna polymerase ii , transcription factor , eukaryotic transcription , cytoplasm , biology , gene , chemistry , promoter , genetics , gene expression , linguistics , philosophy
Many functions have been ascribed to the Ccr4‐Not complex. First described many years ago as a potential regulator of preinitiation complex (PIC) formation, more recently, a large body of evidence indicates it is predominantly cytoplasmic and regulates deadenylation of mRNA and ubiquitylation of substrates in the cytoplasm and nucleus. A direct role of this complex in transcription has not been demonstrated clearly, and the discovery of the cytoplasmic functions of this complex raises questions about how it regulates gene expression. Here we provide conclusive evidence that Ccr4‐Not directly regulates RNAPII transcription elongation. Ccr4‐Not associates with active genes in vivo , and it predominantly associates with the open reading frames of genes in a transcription and RNAPII‐dependent manner. We show that Ccr4‐Not regulates multiple elongation functions, and interestingly, mutation of different subunits of this complex results in distinct elongation phenotypes. Interestingly, Ccr4‐Not associates with RNAPII in a CTD‐independent manner in vitro and in vivo . Furthermore, using a highly purified system, we demonstrate that Ccr4‐Not associates with RNAPII elongation complexes and stimulates transcription elongation. Together, our results bring to light the functions of the Ccr4‐Not complex in the transcription cycle and provide evidence that it contributes directly to transcription by RNAPII.