Endogenous RNA interference is driven by copy number

Elife. 2014 Feb 11:3:e01581. doi: 10.7554/eLife.01581.

Abstract

A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome. DOI: http://dx.doi.org/10.7554/eLife.01581.001.

Keywords: RNA interference; copy number; non-coding RNA; pervasive transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Gene Dosage*
  • Gene Expression Regulation, Fungal*
  • Genome, Fungal
  • RNA Interference*
  • RNA, Fungal / genetics*
  • RNA, Fungal / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic

Substances

  • Argonaute Proteins
  • RNA, Fungal
  • RNA, Messenger
  • RNA, Small Interfering
  • Saccharomyces cerevisiae Proteins
  • Ribonuclease III