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Argonaute2 Is the Catalytic Engine of Mammalian RNAi
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Argonaute2 Is the Catalytic Engine of Mammalian RNAi
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Journal Article
Argonaute2 Is the Catalytic Engine of Mammalian RNAi
2004
Overview
Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes \"Slicer\" activity to RISC, providing the catalytic engine for RNAi.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Biological and medical sciences
/ Central Nervous System - embryology
/ Embryonic and Fetal Development
/ Embryos
/ Eukaryotic Initiation Factor-2
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental
/ Genetics
/ Humans
/ Mammals
/ Mice
/ MicroRNA
/ Oligonucleotide Array Sequence Analysis
/ Peptide Initiation Factors - chemistry
/ Peptide Initiation Factors - metabolism
/ Proteins
/ RNA
/ RNA, Small Interfering - metabolism
/ RNA-Induced Silencing Complex - chemistry
/ RNA-Induced Silencing Complex - metabolism
/ Virology
