The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans

The let-7 microRNA family members mir-48, mir-84, and mir-241 function together to regulate developmental timing in Caenorhabditis elegans
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DOI:
10.1016/j.devcel.2005.07.009
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发表时间:
2005-09-01
期刊:
影响因子:
11.8
通讯作者:
Ambros, V
Ambros, V
中科院分区:
生物学1区
文献类型:
--
作者:
Abbott, AL;Alvarez-Saavedra, E;Ambros, V

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microRNA let-7是C.优美的最近,已经鉴定出与let-7具有序列相似性的microRNA。我们发现,双重突变的动物缺乏let-7家族microRNA基因mir-48和mir-84表现出延迟蜕皮行为和延迟成年基因表达的皮下组织。缺乏mir-48、mir-84和mir-241的三重突变动物除了表现出发育迟缓的成年期事件外,还表现出L2期事件的重复。mir-48、mir-84和mir-241一起起作用以控制L2-至-L3的转变,可能是通过与hbi-13 ′ UTR中的互补位点碱基配对并下调hbi-1活性。遗传分析表明,mir-48、mir-84和mir-241与异时基因lin-28和lin-46平行地指定L2至L3过渡的时间。这些结果表明,let-7家族microRNA的功能组合,以影响早期和晚期发育的时间决定。
The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbi-13 ' UTR and downregulating hbi-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7family microRNAs function in combination to affect both early and late developmental timing decisions.