Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation
Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation
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DOI：
10.1016/j.cell.2005.07.031
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发表时间：
2005-08-26
期刊：
影响因子：
64.5
通讯作者：
Pasquinelli, AE
中科院分区：
文献类型：
--
作者：
Bagga, S;Bracht, J;Pasquinelli, AE
microRNAs（miRNAs）是一种类似于22个核苷酸的RNAs，负调控蛋白质编码基因的表达。在动物中miRNA功能的现有模型中，与其靶标形成不完全双链体的miRNA抑制蛋白质表达而不影响mRNA水平。在这里，我们报告说，在C。在线虫中，let-7 miRNA的调控导致lin-41靶mRNA的降解，尽管其3 'UTR调控序列只能与miRNA部分碱基配对。此外，lin-14和lin-28是lin-4 miRNA的靶点，我们发现这些蛋白质编码基因的mRNA水平响应lin-4表达而显著降低。这项研究表明，含有部分miRNA互补位点的mRNA可以在体内降解，提高了mRNA稳定性水平的调节可能比以前认识到的miRNA途径更常见的可能性。
MicroRNAs (miRNAs) are similar to 22 nucleotide RNAs that negatively regulate the expression of protein-coding genes. In a present model of miRNA function in animals, miRNAs that form imperfect duplexes with their targets inhibit protein expression without affecting mRNA levels. Here, we report that in C. elegans, regulation by the let-7miRNA results in degradation of its lin-41 target mRNA, despite the fact that its 3'UTR regulatory sequences can only partially base-pair with the miRNA. Furthermore, lin-14 and lin-28 are targets of the lin-4 miRNA, and we show that the mRNA levels for these protein-coding genes significantly decrease in response to lin-4 expression. This study reveals that mRNAs containing partial miRNA complementary sites can be targeted for degradation in vivo, raising the possibility that regulation at the level of mRNA stability may be more common than previously appreciated for the miRNA pathway.