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.