title: Staufen Negatively Modulates MicroRNA Activity in Caenorhabditis elegans.
abstract: The double-stranded RNA-binding protein Staufen has been implicated in various posttranscriptional 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 microRNA activity downstream of microRNA biogenesis, possibly by competing with microRNAs for binding on the 3' untranslated region of target mRNAs.
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, 01605.
authors.forename: Zhiji
authors.initials: Z
authors.lastname: Ren
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, 01605.
authors.forename: Isana
authors.initials: I
authors.lastname: Veksler-Lublinsky
authors.affiliation: Intellia Therapeutics Inc., Cambridge, Massachusetts 02139.
authors.forename: David
authors.initials: D
authors.lastname: Morrissey
authors.affiliation: Program in Molecular Medicine, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, Massachusetts, 01605 victor.ambros@umassmed.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D000818:Animals; D064113:CRISPR-Cas Systems; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D000072669:Gene Editing; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D005838:Genotype; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D016601:RNA-Binding Proteins; C579338:stau-1 proteins, C elegans
keywords: 3′UTR; RNA-binding protein; RNAi; microRNA; stau-1