Staufen negatively modulates microRNA activity in Caenorhabditis elegans

Zhiji Ren, Isana Veksler-Lublinsky, David Morrissey, Victor Ambros

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The double-stranded RNA-binding protein Staufen has been implicated in various post-transcriptional gene regulatory processes. Here, we demonstrate that the Caenorhabditis elegans homolog of Staufen, STAU-1, functionally interacts with microRNAs. Loss-of-function mutations of stau-1 significantly suppress phenotypes of let-7 family microRNA mutants, a hypomorphic allele of dicer, and a lsy-6 microRNA partial loss-of-function mutant. Furthermore, STAU-1 modulates the activity of lin-14, a target of lin-4 and let-7 family microRNAs, and this modulation is abolished when the 3' untranslated region of lin-14 is removed. Deep sequencing of small RNA cDNA libraries reveals no dramatic change in the levels of microRNAs or other small RNA populations between wild-type and stau-1 mutants, with the exception of certain endogenous siRNAs in the WAGO pathway. The modulation of microRNA activity by STAU-1 does not seem to be associated with the previously reported enhanced exogenous RNAi (Eri) phenotype of stau-1 mutants, since eri-1 exhibits the opposite effect on microRNA activity. Altogether, our results suggest that STAU-1 negatively modulates micro-RNA activity downstream of microRNA biogenesis, possibly by competing with microRNAs for binding on the 3' untranslated region of target mRNAs.

Original languageEnglish
Pages (from-to)1227-1237
Number of pages11
JournalG3: Genes, Genomes, Genetics
Volume6
Issue number5
DOIs
StatePublished - 1 May 2016
Externally publishedYes

Keywords

  • 3'UTR
  • MicroRNA
  • RNA-binding protein
  • RNAi
  • Stau-1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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