期刊
G3-GENES GENOMES GENETICS
卷 6, 期 5, 页码 1227-1237出版社
OXFORD UNIV PRESS INC
DOI: 10.1534/g3.116.027300
关键词
microRNA; stau-1; RNAi; RNA-binding protein; 3 ' UTR
资金
- National Institutes of Health [NIH] Office of Research Infrastructure Programs [P40 OD010440]
- NIH [R01 GM34028]
- Leukemia and Lymphoma society
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 39 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.
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