MiRNA影响mRNA的机制

2010/08/16 10:49:45

MiRNA影响mRNA的机制

MicroRNA（普遍存在的、调控基因表达的短非编码RNA）已知影响信使RNA (mRNA)和蛋白的水平。但因为蛋白生成依赖于mRNA的存在，所以确定由微RNA调控的mRNA解理与翻译抑制的相对贡献一直有困难。

现在，David Bartel及其同事理清了两个机制之间的关系，并且发现，与人们所预料的相反的是，微RNA主要通过使目标mRNA失去稳定性来发挥作用，而不是通过抑制它们的翻译来发挥作用。这些结果表明，需要对很多以前的结论进行一次重新评估。

Nature doi:10.1038/nature09267

Mammalian microRNAs predominantly act to decrease target mRNA levels

Huili Guo,Nicholas T. Ingolia,Jonathan S. Weissman& David P. Bartel

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.