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

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Chromatin / metabolism
  • Chromatin Assembly and Disassembly
  • Gene Expression Regulation
  • Histones / metabolism
  • RNA Interference*
  • RNA, Small Interfering
  • Transcription, Genetic*

Substances

  • CSR-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Chromatin
  • Histones
  • RNA, Small Interfering

Associated data

  • GEO/GSE49946