PerspectiveRNA

Complete pairing not needed

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Science  31 Oct 2014:
Vol. 346, Issue 6209, pp. 542-543
DOI: 10.1126/science.1262123

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Summary

Gene expression can be silenced in eukaryotic cells by small noncoding RNAs that target mRNAs and prevent their translation into protein. These microRNAs (miRNAs) recruit a ribonucleoprotein complex called the RNA-induced silencing complex (RISC) and guide it to target mRNA, where miRNA-mRNA annealing allows RISC to execute translational repression (see the first figure, panel A). Argonaute (Ago) protein, a key component of RISC, is highly conserved from prokaryotes to eukaryotes and is essential for gene silencing (1). The mechanistic basis underlying the silencing initially emerged from x-ray crystallographic studies of prokaryotic Ago proteins bound as binary complexes to guide strands (DNA) and as ternary complexes with added target strands (RNA or DNA). These structural studies focused on small interfering RNA (siRNA)–mediated cleavage of target mRNA, whereas more recent studies of the same complexes in eukaryotes have focused on miRNA-mediated translational repression (24). On page 608 of this issue, major mechanistic insights are gleaned from structural studies by Schirle et al. (5) on binary and ternary complexes of human Argonaute 2 (hAgo2).