Hierarchical Rules for Argonaute Loading in Drosophila

Czech, B., Zhou, R., Erlich, Y., Brennecke, J., Binari, R., Villalta, C., Gordon, A., Perrimon, N., Hannon, G. J. (2009) Hierarchical Rules for Argonaute Loading in Drosophila. Molecular Cell, 36 (3). pp. 445-456. ISSN 10972765 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/19917252
DOI: 10.1016/j.molcel.2009.09.028

Abstract

Drosophila Argonaute-1 and Argonaute-2 differ in function and small RNA content. AGO2 binds to siRNAs, whereas AGO1 is almost exclusively occupied by microRNAs. MicroRNA duplexes are intrinsically asymmetric, with one strand, the miR strand, preferentially entering AGO1 to recognize and regulate the expression of target mRNAs. The other strand, miR *, has been viewed as a byproduct of microRNA biogenesis. Here, we show that miR *s are often loaded as functional species into AGO2. This indicates that each microRNA precursor can potentially produce two mature small RNA strands that are differentially sorted within the RNAi pathway. miR * biogenesis depends upon the canonical microRNA pathway, but loading into AGO2 is mediated by factors traditionally dedicated to siRNAs. By inferring and validating hierarchical rules that predict differential AGO loading, we find that intrinsic determinants, including structural and thermodynamic properties of the processed duplex, regulate the fate of each RNA strand within the RNAi pathway. © 2009 Elsevier Inc. All rights reserved.

Item Type: Paper
Uncontrolled Keywords: PROTEINS RNA argonaute 1 protein argonaute 2 protein microRNA small interfering RNA article biogenesis controlled study Drosophila nonhuman nucleotide sequence protein analysis protein binding RNA interference RNA structure thermodynamics validation process 3' Untranslated Regions Animals Arabidopsis Proteins Base Pairing Blotting, Northern Cell Line Drosophila melanogaster Drosophila Proteins Immunoprecipitation MicroRNAs Models, Biological Nucleic Acid Conformation RNA Precursors RNA, Double-Stranded RNA, Messenger RNA, Small Interfering RNA-Induced Silencing Complex
Subjects: organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > argonaute proteins
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
CSHL Authors:
Communities: CSHL labs > Hannon lab
Watson School > Publications
Depositing User: Matt Covey
Date Deposited: 09 Jan 2013 16:43
Last Modified: 22 Sep 2014 18:27
PMCID: PMC2795325
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26440

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