title: The multifunctional Ccr4-Not complex directly promotes transcription elongation.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kruk
authors.forename: Arnob
authors.initials: A
authors.lastname: Dutta
authors.forename: Jianhua
authors.initials: J
authors.lastname: Fu
authors.forename: David S
authors.initials: DS
authors.lastname: Gilmour
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Reese
mesh_terms: D015966:Gene Expression Regulation, Fungal; D011485:Protein Binding; D012319:RNA Polymerase II / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035602:Transcriptional Elongation Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D012319:RNA Polymerase II