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A genome-wide map of conserved microRNA targets in C. elegans

Item Type:Article
Title:A genome-wide map of conserved microRNA targets in C. elegans
Creators Name:Lall, S. and Grun, D. and Krek, A. and Chen, K. and Wang, Y.L. and Dewey, C.N. and Sood, P. and Colombo, T. and Bray, N. and Macmenamin, P. and Kao, H.L. and Gunsalus, K.C. and Pachter, L. and Piano, F. and Rajewsky, N.
Abstract:BACKGROUND: Metazoan miRNAs regulate protein-coding genes by binding the 3' UTR of cognate mRNAs. Identifying targets for the 115 known C. elegans miRNAs is essential for understanding their function. RESULTS: By using a new version of PicTar and sequence alignments of three nematodes, we predict that miRNAs regulate at least 10% of C. elegans genes through conserved interactions. We have developed a new experimental pipeline to assay 3' UTR-mediated posttranscriptional gene regulation via an endogenous reporter expression system amenable to high-throughput cloning, demonstrating the utility of this system using one of the most intensely studied miRNAs, let-7. Our expression analyses uncover several new potential let-7 targets and suggest a new let-7 activity in head muscle and neurons. To explore genome-wide trends in miRNA function, we analyzed functional categories of predicted target genes, finding that one-third of C. elegans miRNAs target gene sets are enriched for specific functional annotations. We have also integrated miRNA target predictions with other functional genomic data from C. elegans. CONCLUSIONS: At least 10% of C. elegans genes are predicted miRNA targets, and a number of nematode miRNAs seem to regulate biological processes by targeting functionally related genes. We have also developed and successfully utilized an in vivo system for testing miRNA target predictions in likely endogenous expression domains. The thousands of genome-wide miRNA target predictions for nematodes, humans, and flies are available from the PicTar website and are linked to an accessible graphical network-browsing tool allowing exploration of miRNA target predictions in the context of various functional genomic data resources.
Keywords:Base Sequence, Caenorhabditis elegans, Chromosome Mapping, Computational Biology, Conserved Sequence, Gene Expression Profiling, Gene Expression Regulation, Reporter Genes, Helminth Genome, Genomics, MicroRNAs, Molecular Sequence Data, Sequence Alignment, Animals, Worms
Source:Current Biology
Publisher:Cell Press
Page Range:460-471
Date:7 March 2006
Official Publication:https://doi.org/10.1016/j.cub.2006.01.050
PubMed:View item in PubMed

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