Distinct catalytic and non-catalytic roles of ARGONAUTE4 in RNA-directed DNA methylation

Qi, Y., He, X., Wang, X. J., Kohany, O., Jurka, J., Hannon, G. J. (2006) Distinct catalytic and non-catalytic roles of ARGONAUTE4 in RNA-directed DNA methylation. Nature, 443 (7114). pp. 1008-12. ISSN 1476-4687 (Electronic)

URL: https://www.ncbi.nlm.nih.gov/pubmed/16998468
DOI: 10.1038/nature05198

Abstract

DNA methylation has important functions in stable, transcriptional gene silencing, immobilization of transposable elements and genome organization. In Arabidopsis, DNA methylation can be induced by double-stranded RNA through the RNA interference (RNAi) pathway, a response known as RNA-directed DNA methylation. This requires a specialized set of RNAi components, including ARGONAUTE4 (AGO4). Here we show that AGO4 binds to small RNAs including small interfering RNAs (siRNAs) originating from transposable and repetitive elements, and cleaves target RNA transcripts. Single mutations in the Asp-Asp-His catalytic motif of AGO4 do not affect siRNA-binding activity but abolish its catalytic potential. siRNA accumulation and non-CpG DNA methylation at some loci require the catalytic activity of AGO4, whereas others are less dependent on this activity. Our results are consistent with a model in which AGO4 can function at target loci through two distinct and separable mechanisms. First, AGO4 can recruit components that signal DNA methylation in a manner independent of its catalytic activity. Second, AGO4 catalytic activity can be crucial for the generation of secondary siRNAs that reinforce its repressive effects.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Arabidopsis Proteins chemistry genetics metabolism Catalysis CpG Islands genetics DNA Methylation DNA Plant genetics metabolism Humans Molecular Sequence Data RNA Interference RNA, Plant genetics metabolism RNA SmallInterfering genetics metabolism Sequence Alignment
Subjects: organism description > plant > Arabidopsis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > sRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: CSHL Librarian
Date Deposited: 09 Dec 2011 19:51
Last Modified: 02 Dec 2016 15:24
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22880

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