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Title: Functional small RNAs are generated from select miRNA hairpin loops in flies and mammals
Authors: Okamura, K.
Ladewig, E.
Zhou, L. 
Lai, E.C.
Keywords: Argonaute protein
Mirna hairpin loop
Small RNA loading
Issue Date: 1-Apr-2013
Citation: Okamura, K., Ladewig, E., Zhou, L., Lai, E.C. (2013-04-01). Functional small RNAs are generated from select miRNA hairpin loops in flies and mammals. Genes and Development 27 (7) : 778-792. ScholarBank@NUS Repository.
Abstract: In the canonical animal microRNA (miRNA) pathway, Drosha generates ~60- to 70-nucleotide pre-miRNA hairpins that are cleaved by Dicer into small RNA duplexes that load into Argonaute proteins, which retain a single mature strand in the active complex. The terminal loops of some miRNA hairpins regulate processing efficiency, but once liberated by Dicer, they are generally considered nonfunctional by-products. Here, we show that specific miRNA loops accumulate in effector Argonaute complexes in Drosophila and mediate miRNA-type repression. This was unexpected, since endogenous loading of Argonaute proteins was believed to occur exclusively via small RNA duplexes. Using in vitro assays, which recapitulate Argonaute-specific loop loading from synthetic pre-miRNAs and even single-stranded oligoribonucleotides corresponding to miRNA loops, we reveal that the loop-loading mechanism is distinct from duplex loading. We also show that miRNA loops loaded into the miRNA effector AGO1 are subject to 3' resection, and structure-function analyses indicate selectivity of loop loading. Finally, we demonstrate that select miRNA loops in mammals are similarly loaded into Argonaute complexes and direct target repression. Altogether, we reveal a conserved mechanism that yields functional RNAs from miRNA loop regions, broadening the repertoire of Argonaute-dependent regulatory RNAs and providing evidence for functionality of endogenous ssRNA species. © 2013 by Cold Spring Harbor Laboratory Press.
Source Title: Genes and Development
ISSN: 08909369
DOI: 10.1101/gad.211698.112
Appears in Collections:Staff Publications

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