title: A genome-wide map of conserved microRNA targets in C. elegans.
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.
authors.affiliation: Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
authors.forename: Sabbi
authors.initials: S
authors.lastname: Lall
authors.forename: Dominic
authors.initials: D
authors.lastname: Grün
authors.forename: Azra
authors.initials: A
authors.lastname: Krek
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.forename: Yi-Lu
authors.initials: YL
authors.lastname: Wang
authors.forename: Colin N
authors.initials: CN
authors.lastname: Dewey
authors.forename: Pranidhi
authors.initials: P
authors.lastname: Sood
authors.forename: Teresa
authors.initials: T
authors.lastname: Colombo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bray
authors.forename: Philip
authors.initials: P
authors.lastname: Macmenamin
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Kao
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Gunsalus
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Rajewsky
mesh_terms: 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
chemical_list: D035683:MicroRNAs