title: Dicer promotes transcription termination at sites of replication stress to maintain genome stability.
abstract: Nuclear RNAi is an important regulator of transcription and epigenetic modification, but the underlying mechanisms remain elusive. Using a genome-wide approach in the fission yeast S. pombe, we have found that Dcr1, but not other components of the canonical RNAi pathway, promotes the release of Pol II from the 3? end of highly transcribed genes, and, surprisingly, from antisense transcription of rRNA and tRNA genes, which are normally transcribed by Pol I and Pol III. These Dcr1-terminated loci correspond to sites of replication stress and DNA damage, likely resulting from transcription-replication collisions. At the rDNA loci, release of Pol II facilitates DNA replication and prevents homologous recombination, which would otherwise lead to loss of rDNA repeats especially during meiosis. Our results reveal a novel role for Dcr1-mediated transcription termination in genome maintenance and may account for widespread regulation of genome stability by nuclear RNAi in higher eukaryotes.
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Stephane E
authors.initials: SE
authors.lastname: Castel
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Sonali
authors.initials: S
authors.lastname: Bhattacharjee
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: An-Yun
authors.initials: AY
authors.lastname: Chang
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/Universidad de Salamanca, Salamanca 37007, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Sánchez
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/Universidad de Salamanca, Salamanca 37007, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Valbuena
authors.affiliation: Instituto de Biología Funcional y Genómica, CSIC/Universidad de Salamanca, Salamanca 37007, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Antequera
authors.affiliation: Howard Hughes Medical Institute-Gordon and Betty Moore Foundation, Watson School of Biological Sciences Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: martiens@cshl.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Martienssen
mesh_terms: D004261:DNA Replication; D016373:DNA, Antisense / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism*; D042822:Genomic Instability; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012568:Schizosaccharomyces / Q000201:enzymology / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism*; D061806:Transcription Termination, Genetic; D014158:Transcription, Genetic
chemical_list: D016373:DNA, Antisense; D029702:Schizosaccharomyces pombe Proteins; D012319:RNA Polymerase II; C568524:Dcr1 protein, S pombe; D004722:Endoribonucleases