title: Microprocessor, Setx, Xrn2, and Rrp6 co-operate to induce premature termination of transcription by RNAPII.
abstract: 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.
authors.affiliation: Laboratoires de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, 34396 Montpellier, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Wagschal
authors.forename: Emilie
authors.initials: E
authors.lastname: Rousset
authors.forename: Poornima
authors.initials: P
authors.lastname: Basavarajaiah
authors.forename: Xavier
authors.initials: X
authors.lastname: Contreras
authors.forename: Alex
authors.initials: A
authors.lastname: Harwig
authors.forename: Sabine
authors.initials: S
authors.lastname: Laurent-Chabalier
authors.forename: Mirai
authors.initials: M
authors.lastname: Nakamura
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Oussama
authors.initials: O
authors.lastname: Meziane
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boyer
authors.forename: Hugues
authors.initials: H
authors.lastname: Parrinello
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Christophe
authors.initials: C
authors.lastname: Terzian
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
authors.forename: Rosemary
authors.initials: R
authors.lastname: Kiernan
mesh_terms: D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases; D005095:Exoribonucleases / Q000378:metabolism*; D063326:Exosome Multienzyme Ribonuclease Complex / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D064251:Multifunctional Enzymes; D011401:Promoter Regions, Genetic; D020365:RNA Helicases / Q000378:metabolism*; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D064251:Multifunctional Enzymes; D012367:RNA, Viral; D014157:Transcription Factors; D012319:RNA Polymerase II; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human; C120903:XRN2 protein, human; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases