A genome-wide map of conserved microRNA targets in C. elegans.
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.
Lall
Sabbi
S
Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
Grün
Dominic
D
Krek
Azra
A
Chen
Kevin
K
Wang
Yi-Lu
YL
Dewey
Colin N
CN
Sood
Pranidhi
P
Colombo
Teresa
T
Bray
Nicolas
N
Macmenamin
Philip
P
Kao
Huey-Ling
HL
Gunsalus
Kristin C
KC
Pachter
Lior
L
Piano
Fabio
F
Rajewsky
Nikolaus
N
D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping / Q000379:methods; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049751:Genome, Helminth; D023281:Genomics / Q000379:methods*; D035683:MicroRNAs / Q000502:physiology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D035683:MicroRNAs