Distinct Argonaute-Mediated 22G-RNA Pathways Direct Genome Surveillance in the C. elegans Germline

被引：355

作者：

Gu, Weifeng ^{[1
]}

Shirayama, Masaki ^{[1
]}

Conte, Darryl, Jr. ^{[1
]}

Vasale, Jessica ^{[1
]}

Batista, Pedro J. ^{[1
,3
]}

Claycomb, Julie M. ^{[1
]}

Moresco, James J. ^{[4
]}

Youngman, Elaine M. ^{[1
]}

Keys, Jennifer ^{[1
]}

Stoltz, Matthew J. ^{[1
]}

Chen, Chun-Chieh G. ^{[1
]}

Chaves, Daniel A. ^{[1
,5
]}

Duan, Shenghua ^{[1
]}

Kasschau, Kristin D. ^{[6
]}

Fahlgren, Noah ^{[6
]}

Yates, John R., III ^{[4
]}

Mitani, Shohei ^{[7
,8
]}

Carrington, James C. ^{[6
]}

Mello, Craig C. ^{[1
,2
]}

机构：

[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01606 USA

[2] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA

[3] Gulbenkian PhD Programme Biomed, P-2780156 Oeiras, Portugal

[4] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[5] Univ Lisbon, Inst Mol Med, Fac Med, P-1649028 Lisbon, Portugal

[6] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA

[7] Tokyo Womens Med Univ, Sch Med, Dept Physiol, Tokyo 1628666, Japan

[8] Japan Sci & Technol Agcy, CREST, Tokyo 1628666, Japan

来源：

MOLECULAR CELL | 2009年 / 36卷 / 02期

关键词：

MESSENGER-RNA SURVEILLANCE; SMALL INTERFERING RNAS; CAENORHABDITIS-ELEGANS; ENDOGENOUS SIRNAS; LINE DEVELOPMENT; GENE-EXPRESSION; PROTEIN; POLYMERASE; MICRORNAS; HELICASE;

D O I：

10.1016/j.molcel.2009.09.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.

引用

页码：231 / 244

页数：14

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