Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome

Sneha Rath, Jesse Donovan, Gena Whitney, Alisha Chitrakar, Wei Wang, Alexei Korennykh

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Double-stranded RNA (dsRNA) activates the innate immune system of mammalian cells and triggers intracellular RNA decay by the pseudokinase and endoribonuclease RNase L. RNase L protects from pathogens and regulates cell growth and differentiation by destabilizing largely unknown mammalian RNA targets. We developed an approach for transcriptome-wide profiling of RNase L activity in human cells and identified hundreds of direct RNA targets and nontargets. We show that this RNase L-dependent decay selectively affects transcripts regulated by microRNA (miR)-17/miR-29/miR-200 and other miRs that function as suppressors of mammalian cell adhesion and proliferation. RNase L mimics the effects of these miRs and acts as a suppressor of proliferation and adhesion in mammalian cells. Our data suggest that RNase L-dependent decay serves to establish an antiproliferative state via destabilization of the miR-regulated transcriptome.

Original languageEnglish (US)
Pages (from-to)15916-15921
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number52
DOIs
StatePublished - Dec 29 2015

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Adhesion
  • DsRNA
  • MiR-200
  • MicroRNA
  • RNase L

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