MicroRNAs (miRNAs) are a class of small regulatory RNA that inhibit target gene expression post-transcriptionally. Several hundreds of miRNAs have been discovered in diverse organisms but their biological roles are largely unknown. Caenorhabditis elegans </I> mutants with deletions in most miRNA genes have been generated by a deletion screen (1) as a resource for the study of miRNA function. The mir-51
family of miRNAs is a highly conserved family of six miRNAs that share a ''seed'' region (seven continuous base pairs at their 5'' end at bases 2 to 8). Animals lacking individual members of the mir-51
family of miRNAs show no obvious abnormal phenotypes, likely because these six miRNAs act redundantly. Mutant strains in which multiple mir-51
family members have been deleted show gradually more severe defects in growth rate and development as further family members are deleted, culminating in embryonic or early larval lethality. This series correlates with the relative expression levels of the miRNAs (1). Mutant phenotypes can be rescued by short genomic regions encoding mir-51
family miRNAs. Bioinformatic miRNA target prediction has provided lists of candidate miRNA target mRNAs. These targets are being tested using a combination of RNAi, fluorescent protein reporter constructs and antibodies. In addition, we are carrying out enhancer and suppressor screens to identify direct targets of the mir-51
miRNA family. (1) Miska, E. A., Alvarez-Saavedra, E. A., Abbott, A. L., Lau, N. P., Hellman, A. B., McGonagle, S., Bartel, D. P., Ambros, V. R., Horvitz, H. R. - unpublished results.