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A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans

Lall, Sabbi and Grün, Dominic and Krek, Azra and Chen, Kevin and Wang, Yi-Lu and Dewey, Colin N. and Sood, Pranidhi and Colombo, Teresa and Bray, Nicolas and MacMenamin, Philip and Kao, Huey-Ling and Gunsalus, Kristin C. and Pachter, Lior and Piano, Fabio and Rajewsky, Nikolaus (2006) A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans. Current Biology, 16 (5). pp. 460-471. ISSN 0960-9822. doi:10.1016/j.cub.2006.01.050.

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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.

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Pachter, Lior0000-0002-9164-6231
Additional Information:© 2006 Elsevier. Received 19 December 2005, Revised 19 January 2006, Accepted 24 January 2006, Available online 2 February 2006. We would like to thank Marc Vidal and Denis Dupuy for their kind gift of promoterome constructs used in this study. In addition, we would like to thank Anita Fernandez for discussions and comments on the manuscript and Frank Slack and Oliver Hobert for help with Table S1. We thank Thadeous Kacmarczyk for administration of our computers. We also thank Tamer A. Hadi for excellent technical support for this project. D.G. was funded by a scholarship from the German Academic Exchange Service. This work was supported by NIH Grants R21-HD049435 to N.R. and F.P. and R01-HD046236 to F.P. and by a HHMI grant through the Undergraduate Biological Sciences Education Program to NYU. L.P. is supported by Sloan Research Fellowship, NSF grant CCF 03-47992, and L.P., C.N.D., N.B., and K.C. are supported by NIH Grant R01-HG02362.
Funding AgencyGrant Number
Deutscher Akademischer Austauschdienst (DAAD)UNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20170307-164849681
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Official Citation:Sabbi Lall, Dominic Grün, Azra Krek, Kevin Chen, Yi-Lu Wang, Colin N. Dewey, Pranidhi Sood, Teresa Colombo, Nicolas Bray, Philip MacMenamin, Huey-Ling Kao, Kristin C. Gunsalus, Lior Pachter, Fabio Piano, Nikolaus Rajewsky, A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans, Current Biology, Volume 16, Issue 5, 7 March 2006, Pages 460-471, ISSN 0960-9822, ( Keywords: RNA
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74877
Deposited By: George Porter
Deposited On:08 Mar 2017 15:49
Last Modified:15 Nov 2021 16:28

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