期刊
EMBO REPORTS
卷 12, 期 5, 页码 415-420出版社
WILEY
DOI: 10.1038/embor.2011.48
关键词
Argonaute; miRNA; MID domain; cap; translational repression
资金
- Canada Research Chair
- Canadian Institutes of Health Research (CIHR) [MOP-82929]
- Boehringer Ingelheim Fonds PhD Fellowship
- Howard Hughes Medical Institute [55005604]
- Polish Ministry of Science and Higher Education [N N301 096339]
- Human Frontiers Science Program [0018/2006-C/1]
In RNA silencing, microRNA (miRNA)-mediated translational repression occurs through mechanisms that do not invoke messenger-RNA (mRNA) target cleavage by Argonaute proteins. The nature of these mechanisms is unclear, but several recent studies have proposed that a direct interaction between the mRNA-cap and the middle (MID) domain of Argonautes is involved. Here, we present crystallographic and NMR data demonstrating that cap analogues do not bind significantly to the isolated MID domain of human Argonaute 2 (hAGO2) and are found in the miRNA 5'-nucleotide binding site in an implausible binding mode. Additionally, in vitro pull-down experiments with full-length hAGO2 indicate that the interaction with cap analogues is nonspecific.
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