Chan Shih-Peng, Slack Frank J
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Dev Biol. 2009 Oct 1;334(1):152-60. doi: 10.1016/j.ydbio.2009.07.011. Epub 2009 Jul 21.
The let-7 microRNA (miRNA) regulates developmental timing at the larval-to-adult transition in Caenorhabditis elegans. Dysregulation of let-7 results in irregular hypodermal and vulval development. Disrupted let-7 function is also a feature of human lung cancer. However, little is known about the mechanism and co-factors of let-7. Here we demonstrate that ribosomal protein RPS-14 is able to modulate let-7 function in C. elegans. The RPS-14 protein co-immunoprecipitated with the nematode Argonaute homolog, ALG-1. Reduction of rps-14 gene expression by RNAi suppressed the aberrant vulva and hypodermis development phenotypes of let-7(n2853) mutant animals and the mis-regulation of a reporter bearing the lin-41 3'UTR, a well established let-7 target. Our results indicate an interactive relationship between let-7 miRNA function and ribosomal protein RPS-14 in regulation of terminal differentiation that may help in understanding the mechanism of translational control by miRNAs.
let-7微小RNA（miRNA）调控秀丽隐杆线虫从幼虫到成虫转变过程中的发育时间。let-7失调会导致不规则的皮下组织和外阴发育。let-7功能紊乱也是人类肺癌的一个特征。然而，关于let-7的机制和辅助因子知之甚少。在这里，我们证明核糖体蛋白RPS-14能够调节秀丽隐杆线虫中的let-7功能。RPS-14蛋白与线虫AGO同源物ALG-1进行了共免疫沉淀。通过RNA干扰降低rps-14基因表达，抑制了let-7(n2853)突变动物异常的外阴和皮下组织发育表型，以及带有lin-41 3'UTR（一个已明确的let-7靶标）的报告基因的失调。我们的结果表明，let-7 miRNA功能与核糖体蛋白RPS-14在终末分化调控中存在相互作用关系，这可能有助于理解miRNA的翻译控制机制。
