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Cell Cycle. 2010 Nov 15;9(22):4455-60. Epub 2010 Nov 15.

Dicer-independent, Ago2-mediated microRNA biogenesis in vertebrates.

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  • 1Sloan-Kettering Institute, Department of Developmental Biology, Cornell University, New York, NY, USA.

Abstract

A canonical biogenesis pathway involving sequential cleavage by the Drosha and Dicer RNAse III enzymes governs the maturation of most animal microRNAs. However, there exist a variety of alternative miRNA biogenesis pathways, most of which bypass Drosha processing. Recently, three groups described for the first time a vertebrate microRNA pathway that bypasses Dicer cleavage. This mechanism was characterized with respect to the highly conserved vertebrate gene mir-451, for which Drosha processing yields a short (42 nucleotide) hairpin that is directly loaded into Ago2, the sole vertebrate "Slicer" Argonaute. Ago2-mediated cleavage of this hairpin yields a 30 nucleotide intermediate, whose 3' end is resected to generate the dominantly cloned ~23 nucleotide mature miR-451. Knowledge of this pathway provides an unprecedented tool with which to express microRNAs and small interfering RNAs in Dicer mutant cells. More generally, the mir-451 backbone constitutes a new platform for gene silencing that complements existing shRNA technology.

PMID:
21088485
[PubMed - indexed for MEDLINE]
PMCID:
PMC3048044
Free PMC Article

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