Argonaute2 Is the Catalytic Engine of Mammalian RNAi
Copyright policy )Argonaute2 Is the Catalytic Engine of Mammalian RNAi
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.
- University of North Carolina at Chapel Hill United States
- Watson School of Biological Sciences United States
- Stony Brook University United States
- Cold Spring Harbor Laboratory United States
- Korea Advanced Institute of Science and Technology Korea (Republic of)
Central Nervous System, Gene Expression Profiling, Eukaryotic Initiation Factor-2, Molecular Sequence Data, Gene Expression Regulation, Developmental, Catalysis, Cell Line, Embryonic and Fetal Development, Mice, MicroRNAs, Mutagenesis, Insertional, Peptide Initiation Factors, Argonaute Proteins, Animals, Humans, Point Mutation, Amino Acid Sequence, Cells, Cultured, In Situ Hybridization, Oligonucleotide Array Sequence Analysis
Central Nervous System, Gene Expression Profiling, Eukaryotic Initiation Factor-2, Molecular Sequence Data, Gene Expression Regulation, Developmental, Catalysis, Cell Line, Embryonic and Fetal Development, Mice, MicroRNAs, Mutagenesis, Insertional, Peptide Initiation Factors, Argonaute Proteins, Animals, Humans, Point Mutation, Amino Acid Sequence, Cells, Cultured, In Situ Hybridization, Oligonucleotide Array Sequence Analysis
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