Journal
EMBO JOURNAL
Volume 29, Issue 19, Pages 3272-3285Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2010.208
Keywords
antisense RNA; let-7; long non-coding RNA; microRNA; primary microRNA
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Funding
- NIH [R01-HL081612]
- WM Keck foundation
- Baxter and Terman faculty awards
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Major RNA products of a microRNA (miRNA) gene-the long primary transcript (pri-miRNA), the similar to 70-nucleotide (nt) precursor miRNA (pre-miRNA), and the similar to 21-nt mature miRNA-all contain the same sequence required for target gene recognition. Thus, it is intrinsically difficult to discern the contribution of individual RNA species or to rule out a function of miRNA precursor species in target repression. Here, we describe a novel approach to dissect the functional contribution of pri-miRNA without compromising important cellular pathways. We show that pri-let-7 has a direct function in target repression in the absence of properly processed mature let-7. Moreover, we show that loop nucleotides provide regulatory controls of the activity of pri-let-7 by modulating interactions between pri-let-7 and target RNAs in vitro and in vivo. Finally, we show that human let-7a-3 pri-miRNA can directly interact with target mRNAs. These findings illustrate that the regulatory information encoded in structured pri-miRNAs may be translated into function through direct interactions with target mRNAs. The EMBO Journal (2010) 29, 3272-3285. doi:10.1038/emboj.2010.208; Published online 31 August 2010
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