Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans
Multiple mechanisms are involved in regulating the expression of the developmental timing regulator lin-28 in Caenorhabditis elegans
复制标题
DOI：
10.1038/sj.emboj.7601451
复制
发表时间：
2006-12-13
期刊：
影响因子：
11.4
通讯作者：
Han, Min
中科院分区：
文献类型：
--
作者：
Morita, Kiyokazu;Han, Min
秀丽隐杆线虫的胚胎后发育程序的时间由一组所谓的异时基因调节，其中包括指定第二幼虫程序的 lin-28。本文描述的 lin-66 突变导致外阴和缝细胞分化延迟，表明 lin-66 在时间调节中的作用。 daf-12/核受体或alg-1/argonaute的突变显着增强了lin-66突变体的迟缓表型，而这些表型被lin-28无效等位基因抑制。我们进一步表明，LIN-28 蛋白水平在 lin-66 突变体中上调，并且这种调节是由 lin-28 的 30UTR 介导的。我们还在 lin-28 30UTR 中发现了一个潜在的 daf-12 响应元件，并表明两个 microRNA (miRNA)（lin-4 和 let-7）结合位点介导了可能不依赖于 lin-66 的冗余抑制活性。定量 PCR 数据表明 lin-28 mRNA 水平受 lin-14 和 miRNA 调节的影响，但不受 daf-12 和 lin-66 调节的影响。这些结果表明lin-28的表达受到多种独立机制的调节，包括LIN-14介导的mRNA水平上调、miRNA介导的RNA降解、LIN-66介导的翻译抑制和DAF-12参与的翻译促进。
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 30UTR of lin-28. We have also identified a potential daf-12-response element within lin-28 30UTR 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.