Research Article

Structural basis for microRNA targeting

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Science  31 Oct 2014:
Vol. 346, Issue 6209, pp. 608-613
DOI: 10.1126/science.1258040

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Repressing the right (and not the wrong) mRNA

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting a repressor complex to specific messenger RNAs (mRNAs). Schirle et al. determined structures of a miRNA bound to both the central component of the repressor complex, the protein Argonaute-2 (Ago2), and a target mRNA (see the Perspective by Patel). The miRNA in the complex first recognizes a short region of complementary sequence in the mRNA. This initial interaction promotes structural changes that allow the complex to bind additional target sequences. The authors suggest that in the absence of extensive miRNA-mRNA pairing, the repressor complex active site is rendered inactive, preventing repression of nontarget mRNAs.

Science, this issue p. 608; see also p. 542