A deletion screen (1) has developed a resource of mutants carrying deletions in most C. elegans microRNAs (miRNAs), short regulatory RNAs that act to repress gene expression post-transcriptionally. The function of most miRNAs in C. elegans is unknown and the majority of mutants show no gross abnormal phenotype (1). The miR-51 family is a redundant and conserved family of six miRNAs whose putative promoters drive GFP in overlapping but not identical spatial patterns. Mutants lacking multiple members of the miR-51 family show gradually more severe defects in growth and animals lacking all members of the family arrest as larvae with an unattached pharynx (Pun) phenotype. These mutant phenotypes can be rescued by short genomic regions encoding any of the miR-51 family miRNAs, demonstrating their redundancy. The pharynx of C. elegans forms from a ball of cells specified in the interior of the developing embryo and extends anteriorly to attach to the hypodermis (2). This attachment requires the arcade cells, which become polarised during pharyngeal attachment and form a continuous epithelium between the pharyngeal and hypodermal cells (2). In the early development of mir-51
family mutant larvae, this epithelium is labelled with a DLG-1-mCHERRY fusion protein indicating that the arcade cells have polarised. However, the attachment of the cells to the pharynx is not maintained and arcade cells separate from the anterior pharynx. We have identified the first target mRNA of the miR-51 family of microRNAs as the cadherin, cdh-3
. A reporter for cdh-3
drives GFP expression in the arcade cells and the 3''UTR of cdh-3
mRNA confers direct regulation by the miR-51 family of miRNAs. However, mutations in cdh-3
(RNAi) fail to suppress the Pun phenotype, suggesting the regulation of a network of miR-51 family target mRNAs is important in the maintenance of pharyngeal attachment. (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. - PLoS Genetics, 2007) (2) Portereiko, M.F., Mango, S.E. - Developmental Biology (2001).