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Nat Struct Mol Biol. 2014 Apr;21(4):358-65. doi: 10.1038/nsmb.2801. Epub 2014 Mar 30.

Global effects of the CSR-1 RNA interference pathway on the transcriptional landscape.

Author information

1
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, USA.
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
3
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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.

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PMID:
24681887
PMCID:
PMC4068146
DOI:
10.1038/nsmb.2801
[Indexed for MEDLINE]
Free PMC Article

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