Misexpression of the Caenorhabditis elegans miRNA let-7 is sufficient to drive developmental programs.
The Caenorhabditis elegans microRNAs (miRNAs) lin-4 and let-7 promote transitions between stage-specific events in development by down-regulating the translation of their target genes. Expression of let-7 is required at the fourth larval stage for the proper transition from larval to differentiated, adult fates in the hypodermis; however, it was not known whether expression of let-7 is sufficient to specify these adult fates. To test this, we created fusion genes between lin-4 and let-7 that direct the expression of let-7 two stages early, at the L2 stage. We find that animals bearing the fusion genes show precocious adult development at the L4 stage, indicating that temporal misexpression of let-7 is sufficient to direct the larval-to-adult transition. Additionally, an RNA interference (RNAi)-based screen for enhancers of the precocious phenotype identified the period ortholog lin-42, among other genes, which are candidate modulators of the effects of let-7 expression. let-7 is conserved throughout bilaterian phylogeny, and orthologs of its targets have roles in vertebrate development, suggesting the importance of understanding how let-7 promotes terminal differentiation in C. elegans and other organisms.
Hayes
G D
GD
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Ruvkun
G
G
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D050939:Gene Fusion; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D018510:RNA, Helminth / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C095571:LIN-29 protein, C elegans; D035683:MicroRNAs; D018510:RNA, Helminth; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans; C452194:lin-4 microRNA, C elegans