期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 17, 期 2, 页码 173-U6出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.1745
关键词
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资金
- Genetics Training Program at the University of California, San Diego
- Genentech
- US National Institutes of Health [GM071654-01, HG004659, GM084317]
- Keck, Searle, V.
- Emerald and Peter Gruber Foundations
- Stem Cell Program at the University of California, San Diego
MicroRNAs (miRNAs) regulate gene expression by guiding Argonaute proteins to specific target mRNA sequences. Identification of bona fide miRNA target sites in animals is challenging because of uncertainties regarding the base-pairing requirements between miRNA and target as well as the location of functional binding sites within mRNAs. Here we present the results of a comprehensive strategy aimed at isolating endogenous mRNA target sequences bound by the Argonaute protein ALG-1 in C. elegans. Using cross-linking and ALG-1 immunoprecipitation coupled with high-throughput sequencing (CLIP-seq), we identified extensive ALG-1 interactions with specific 3' untranslated region (UTR) and coding exon sequences and discovered features that distinguish miRNA complex binding sites in 3' UTRs from those in other genic regions. Furthermore, our analyses revealed a striking enrichment of Argonaute binding sites in genes important for miRNA function, suggesting an autoregulatory role that may confer robustness to the miRNA pathway.
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