title: Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.
abstract: Argonaute proteins and their small RNA cofactors short interfering RNAs are known to inhibit gene expression at the transcriptional and post-transcriptional levels. In Caenorhabditis elegans, the Argonaute CSR-1 binds thousands of endogenous siRNAs (endo-siRNAs) that are antisense to germline transcripts. However, its role in gene expression regulation remains controversial. Here we used genome-wide profiling of nascent RNA transcripts and found that the CSR-1 RNA interference pathway promoted sense-oriented RNA polymerase II transcription. Moreover, a loss of CSR-1 function resulted in global increase in antisense transcription and ectopic transcription of silent chromatin domains, which led to reduced chromatin incorporation of centromere-specific histone H3. On the basis of these findings, we propose that the CSR-1 pathway helps maintain the directionality of active transcription, thereby propagating the distinction between transcriptionally active and silent genomic regions.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
authors.forename: Germano
authors.initials: G
authors.lastname: Cecere
authors.affiliation: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoersch
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: O'Keeffe
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
authors.forename: Alla
authors.initials: A
authors.lastname: Grishok
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D014158:Transcription, Genetic
chemical_list: C544459:CSR-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D006657:Histones; D034741:RNA, Small Interfering