The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans
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DOI：
10.1038/35002607
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发表时间：
2000-02-24
期刊：
影响因子：
64.8
通讯作者：
Ruvkun, G
中科院分区：
文献类型：
--
作者：
Reinhart, BJ;Slack, FJ;Ruvkun, G
梭线虫异时基因途径由一系列调节基因组成，这些基因在时间上受到控制，以指定发育事件的时间（1）。异时基因突变导致细胞命运的时间转换，其中阶段特异性事件被省略或重复（2）。在这里，我们表明，let-7是一个异时开关基因。let-7基因活性的丧失导致幼虫期细胞命运的重复，而let-7基因剂量的增加导致幼虫期成熟命运的早熟表达。let-7编码一种时间调节的21-核苷酸RNA，该RNA与异时基因lin-14、lin-28、lin-41、lin-42和daf-12的3 ′非翻译区中的元件互补，表明这些基因的表达可能直接受let-7控制。携带lin-41 3'非翻译区的报告基因以let-7依赖的方式进行时间调节。第二种调节RNA lin-4通过RNA-RNA相互作用与lin-14和lin-28的3'非翻译区负调控lin-14和lin-28（3，4）。我们建议，顺序阶段特异性表达的lin-4和let-7调节RNA触发过渡的异时调节蛋白的互补，以协调发展的时间。
The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events(1). Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated(2). Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3' untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3' untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions(3,4). We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.