Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans

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Abstract
The timing of postembryonic developmental programs in Caenorhabditis elegans is regulated by a set of so‐called heterochronic genes, including lin‐28 that specifies second larval programs. lin‐66 mutations described herein cause delays in vulval and seam cell differentiation, indicating a role for lin‐66 in timing regulation. A mutation in daf‐12/nuclear receptor or alg‐1/argonaute dramatically enhances the retarded phenotypes of the lin‐66 mutants, and these phenotypes are suppressed by a lin‐28 null allele. We further show that the LIN‐28 protein level is upregulated in the lin‐66 mutants and that this regulation is mediated by the 3′UTR of lin‐28. We have also identified a potential daf‐12‐response element within lin‐28 3′UTR and show that two microRNA (miRNA) (lin‐4 and let‐7)‐binding sites mediate redundant inhibitory activities that are likely lin‐66‐independent. Quantitative PCR data suggest that the lin‐28 mRNA level is affected by lin‐14 and miRNA regulation, but not by daf‐12 and lin‐66 regulation. These results suggest that lin‐28 expression is regulated by multiple independent mechanisms including LIN‐14‐mediated upregulation of mRNA level, miRNAs‐mediated RNA degradation, LIN‐66‐mediated translational inhibition and DAF‐12‐involved translation promotion.