期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms9864
关键词
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资金
- US National Institutes of Health, NINDS [NS034389, NS081706]
- NCI [CA057973]
- NIAID [AI091707, AI090055]
- Office of the Director through the NIH Roadmap for Medical Research [DK085713]
- Starr Foundation
- Simons Foundation [SFARI 240432]
- Jane Coffin Childs Memorial Fund
- Danish Council for Independent Research
- David Rockefeller Graduate Student Fellowship
microRNAs (miRNAs) act as sequence-specific guides for Argonaute (AGO) proteins, which mediate posttranscriptional silencing of target messenger RNAs. Despite their importance in many biological processes, rules governing AGO-miRNA targeting are only partially understood. Here we report a modified AGO HITS-CLIP strategy termed CLEAR (covalent ligation of endogenous Argonaute-bound RNAs)-CLIP, which enriches miRNAs ligated to their endogenous mRNA targets. CLEAR-CLIP mapped similar to 130,000 endogenous miRNA-target interactions in mouse brain and similar to 40,000 in human hepatoma cells. Motif and structural analysis define expanded pairing rules for over 200 mammalian miRNAs. Most interactions combine seed-based pairing with distinct, miRNA-specific patterns of auxiliary pairing. At some regulatory sites, this specificity confers distinct silencing functions to miRNA family members with shared seed sequences but divergent 3'-ends. This work provides a means for explicit biochemical identification of miRNA sites in vivo, leading to the discovery that miRNA 3'-end pairing is a general determinant of AGO binding specificity.
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