Argonaute loading improves the 5' precision of both MicroRNAs and their miRNA* strands in flies.

Current Biology : CB
Hervé SeitzPhillip D Zamore

Abstract

MicroRNAs (miRNAs) are short regulatory RNAs that direct repression of their mRNA targets. The miRNA "seed"-nucleotides 2-7-establishes target specificity by mediating target binding. Accurate processing of the miRNA 5' end is thought to be under strong selective pressure because a shift by just one nucleotide in the 5' end of a miRNA alters its seed sequence, redefining its repertoire of targets (Figure 1). Animal miRNAs are produced by the sequential cleavage of partially double-stranded precursors by the RNase III endonucleases Drosha and Dicer, thereby generating a transitory double-stranded intermediate comprising the miRNA paired to its partially complementary miRNA* strand. Here, we report that in flies, the 5' ends of miRNAs and miRNA* strands are typically more precisely defined than their 3' ends. Surprisingly, the precision of the 5' ends of both miRNA and miRNA* sequences increases after Argonaute2 (Ago2) loading. Our data imply that either many miRNA* sequences are under evolutionary pressure to maintain their seed sequences-that is, they have targets-or that secondary constraints, such as the sequence requirements for loading small RNAs into functional Argonaute complexes, narrow the range of miRNA and miRNA 5' en...Continue Reading

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Citations

May 25, 2011·Cellular and Molecular Life Sciences : CMLS·Julia Starega-RoslanWlodzimierz J Krzyzosiak
Jul 3, 2010·Molecular Genetics and Genomics : MGG·Keita MiyoshiHaruhiko Siomi
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May 27, 2008·Nature Structural & Molecular Biology·Katsutomo OkamuraEric C Lai
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