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Multiple mechanisms are involved in regu ... in-28 in Caenorhabditis elegans
Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans.
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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.
Morita K, Han M
The EMBO journal
2006-12-13 00:00
25
24
5794-804
3' Untranslated Regions,Animals,Caenorhabditis elegans,Caenorhabditis elegans Proteins,Cell Differentiation,Cell Division,Female,Gene Expression Regulation, Developmental,Intercellular Signaling Peptides and Proteins,MicroRNAs,Mutation,Nuclear Proteins,Phenotype,Receptor Protein-Tyrosine Kinases,Receptors, Cytoplasmic and Nuclear,Recombinant Fusion Proteins,Repressor Proteins,Response Elements,Time Factors,Vulva,3' Untranslated Regions,Caenorhabditis elegans Proteins,DAF-12 protein, C elegans,Egl-17 protein, C elegans,Intercellular Signaling Peptides and Proteins,LIN-14 protein, C elegans,LIN-28 protein, C elegans,MicroRNAs,Nuclear Proteins,Receptors, Cytoplasmic and Nuclear,Recombinant Fusion Proteins,Repressor Proteins,Receptor Protein-Tyrosine Kinases
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado, Boulder, CO 80309, USA
EMBO J.
NIGMS GM 47869
0261-4189
10.1038/sj.emboj.7601451
7601451
501
True
17139256
