The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25.

Gabriel D Hayes,Gary Ruvkun,Alison R Frand

doi:10.1242/dev.02655

Gabriel D Hayes, Gary Ruvkun + Show 1 more

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https://doi.org/10.1242/dev.02655

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Abstract

The let-7 microRNA (miRNA) gene of Caenorhabditis elegans controls the timing of developmental events. let-7 is conserved throughout bilaterian phylogeny and has multiple paralogs. Here, we show that the paralog mir-84 acts synergistically with let-7 to promote terminal differentiation of the hypodermis and the cessation of molting in C. elegans. Loss of mir-84 exacerbates phenotypes caused by mutations in let-7, whereas increased expression of mir-84 suppresses a let-7 null allele. Adults with reduced levels of mir-84 and let-7 express genes characteristic of larval molting as they initiate a supernumerary molt. mir-84 and let-7 promote exit from the molting cycle by regulating targets in the heterochronic pathway and also nhr-23 and nhr-25, genes encoding conserved nuclear hormone receptors essential for larval molting. The synergistic action of miRNA paralogs in development may be a general feature of the diversified miRNA gene family.

Highlights

MicroRNAs constitute a large class of small (~22 nt) noncoding RNAs present across eukaryotic phylogeny
RESULTS mir-84 acts together with let-7 to promote the cessation of molting To explore the function of microRNAs paralogous to let-7, we studied the mir-84 gene of C. elegans
We considered that mir-84 and let-7 might target additional genes that promote molting and examined the predicted 3Ј untranslated region (UTR) (Hajarnavis et al, 2004) of 47 genes identified as essential for completion of the larval molts through a genome-wide RNAi screen (Frand et al, 2005 and Table 1 within)

Summary

Introduction

MicroRNAs (miRNAs) constitute a large class of small (~22 nt) noncoding RNAs present across eukaryotic phylogeny. In Caenorhabditis elegans, miRNAs were discovered through genetics (Johnston and Hobert, 2003; Lee et al, 1993; Reinhart et al, 2000), cloning (Lau et al, 2001; Lim et al, 2003) and bioinformatic prediction (Ambros et al, 2003; Grad et al, 2003; Lim et al, 2003). Most of the few metazoan miRNAs studied to date negatively regulate the expression of protein-coding genes by binding imperfectly complementary sites in the 3Ј untranslated region (UTR) of the target mRNA and inhibiting translation (Lee et al, 1993; Olsen and Ambros, 1999; Wightman et al, 1993). Some miRNAs previously thought to act primarily by blocking translation cause some degradation of their target transcripts (Bagga et al, 2005)

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