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First published online 12 August 2009
doi: 10.1242/dev.039008

Development 136, 3043-3055 (2009)
Published by The Company of Biologists 2009
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Systematic analysis of dynamic miRNA-target interactions during C. elegans development

Liang Zhang1,*, Molly Hammell2, Brian A. Kudlow1, Victor Ambros2 and Min Han1,{dagger}

1 Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309, USA.
2 Program in Molecular Medicine, University of Massachusetts School of Medicine, Worcester, MA 01605, USA.

{dagger} Author for correspondence (mhan{at}colorado.edu)

Accepted 24 June 2009

Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA family-mRNA pairs with temporally correlated patterns of AIN-2 association, we gained valuable information on the principles of physiological miRNA::target recognition and predicted 1589 high-confidence miRNA family::mRNA interactions. Our data support the idea that miRNAs preferentially target genes involved in signaling processes and avoid genes with housekeeping functions, and that miRNAs orchestrate temporal developmental programs by coordinately targeting or avoiding genes involved in particular biological functions.

Key words: GW182, AIN-1, AIN-2, miRISCs, Target recognition, Seed matches, Protein glycosylations


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Development 2009 136: e1803. [Full Text]  





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