Molecular Biology

Hooked on Interference

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Science  26 Oct 2007:
Vol. 318, Issue 5850, pp. 535-537
DOI: 10.1126/science.318.5850.535d

Argonaute (Ago) proteins are the effectors that lie at the heart of RNA interference. They bind small interfering (si) or micro (mi) RNAs and use them to target and to repress (in most cases) complementary RNAs, either directly, at the posttranscriptional stage, or indirectly (in the case of some siRNAs) at the transcriptional stage. In fission yeast, transcriptional gene silencing (TGS) is mediated by the RITS complex, which includes the Ago1 and Tas3 proteins. Till et al. have dissected the interaction between Tas3 and Ago1 and find a peptide motif, which they call the Ago hook, in Tas3 that interacts both in vitro and in vivo with the PIWI domain in Ago1. The hook binds in a conserved pocket within the Ago PIWI domain; this same pocket binds the 5′ end of the siRNA/miRNA guide strand. The hook is required for TGS in vivo in fission yeast and can block Drosophila miRNA-mediated repression in vitro. Furthermore, a human Ago-interacting protein harbors a motif that is similar in sequence and in function. The hook is likely to be pivotal in recruiting Ago proteins to specific subcellular locations and in influencing the binding of siRNAs and miRNAs, and thus may determine the functional output of the various Ago complexes. — GR

Nat. Struct. Mol. Biol. 14, 897 (2007).

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