Presentation/Session Information

Session Information

Session Title: RNA Interference, Noncoding RNAs, and Genetic Technologies Session Type: Parallel
Session Location: Carnesale Palisades Ballroom Session Time: Sat, Jun 27 8:30AM - 11:30AM

Presentation Information

Program Number: 140 Presentation Time: 8:54AM - 9:06AM

Presentation Content

Staufen negatively modulates microRNA activity in Caenorhabditis elegans.Zhiji Ren 1,2, Isana Veksler-Lublinsky 1,2, Alejandro Vasquez-Rifo 1,2, David Morrissey 3, Victor Ambros 1,2. 1)Molecular Med, Univ Mass Medical School, Worcester, MA; 2)RNA Therapeutics Institute, Univ Mass Medical School, Worcester, MA; 3)Intellia Therapeutics, Inc. Cambridge, MA

MicroRNAs (miRNAs) are endogenous non-coding small RNAs that post-transcriptionally regulate gene expression primarily through binding to the 3’ untranslated region (3’UTR) of target mRNAs, which results in translation inhibition and/or mRNA degradation. MiRNAs are known to play important roles in various developmental and physiological processes. Staufen is a double-stranded RNA binding protein that has been shown in Drosophila and mammals to regulate mRNA localization, translation and decay. There is only one Staufen homolog identified in C. elegans (stau-1), and the mutants of stau-1 have been shown to exhibit enhanced exogenous RNAi phenotypes and slight germline defects.

Here we demonstrate that loss-of-function mutations of stau-1 increase miRNA activity for several miRNA families. First, both stau-1(tm2266) and stau-1(q798) suppress the developmental timing defects of a let-7 family mutant, mir-48 mir-241(nDf51). In addition, stau-1(tm2266) suppresses the phenotype of a lsy-6 hypomorphic allele (ot150) in a set of bilaterally symmetric gustatory neurons (ASEL/R). Finally, stau-1(tm2266) suppresses the heterochronic phenotype of lin-4(e912); lin-14(n719) animals. Interestingly, stau-1(tm2266) does not suppress the heterochronic phenotype of the 3’UTR deletion mutant lin-14(n355n679), which removes all the predicated binding sites for lin-4 and let-7 family miRNAs. Furthermore, small RNA high-throughput sequencing analysis reveals that there is no dramatic change in most small RNA population between wild type and stau-1(tm2266), except several endogenous siRNAs in the WAGO pathway. The modulation of stau-1 on miRNA activity does not seem to be simply caused by the enhanced exogenous RNAi phenotype of stau-1 mutants since eri-1(mg366) does not suppress, but rather enhances the heterochronic phenotypes of mir-48 mir-241(nDf51) animals. Therefore, our results suggest that STAU-1 negatively modulates miRNA activity downstream of biogenesis, possibly by competing with miRNAs for binding to target mRNA 3’UTRs.

Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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