Structural basis for piRNA 2 '-O-methylated 3 '-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains
Open Access
- 17 January 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (3), 903-910
- https://doi.org/10.1073/pnas.1017762108
Abstract
Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2'-OCH3) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role in genome defense against transposable elements, thereby protecting the genome against transposon-induced defects in gametogenesis and fertility. Humans contain four Piwi family proteins designated Hiwi1, Hiwi2, Hiwi3, and Hili. We report on the structures of Hili-PAZ (Piwi/Argonaute/Zwille) domain in the free state and Hiwi1 PAZ domain bound to self-complementary 14-mer RNAs (12-bp + 2-nt overhang) containing 2'-OCH3 and 2'-OH at their 3' ends. These structures explain the molecular basis underlying accommodation of the 2'-OCH3 group within a preformed Hiwi1 PAZ domain binding pocket, whose hydrophobic characteristics account for the preferential binding of 2'-OCH3 over 2'-OH 3' ends. These results contrast with the more restricted binding pocket for the human Ago1 PAZ domain, which exhibits a reverse order, with preferential binding of 2'-OH over 2'-OCH3 3' ends.This publication has 40 references indexed in Scilit:
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