Connerty Patrick, Bajan Sarah, Remenyi Judit, Fuller-Pace Frances V, Hutvagner Gyorgy
Faculty of Science, University of Technology, Sydney, Australia.
Faculty of Engineering and Information Technology, Centre of Health Technologies, University of Technology, Sydney, Australia.
Biochim Biophys Acta. 2016 Oct;1859(10):1299-305. doi: 10.1016/j.bbagrm.2016.07.013. Epub 2016 Jul 28.
MicroRNAs (miRNAs) are short (21-23nt long) RNAs that post-transcriptionally regulate gene expression in plants and animals. They are key regulators in all biological processes. In mammalian cells miRNAs are loaded into one of the four members of the Argonaute (Ago) protein family to form the RNA-induced silencing complex (RISC). RISCs inhibit the translation of mRNAs that share sequence complementarity with their loaded miRNAs. miRNA processing and miRNA-mediated gene regulation are highly regulated processes and involve many RNA-binding proteins as auxiliary factors. Here we show that the two RNA-binding proteins, p72 and KHSRP, both with known roles in promoting miRNA biogenesis, regulate the protein level of human Ago2 in transformed human cells. We determined that p72 and KHSRP influence Ago2 stability by regulating miRNA levels in the cell and that loss of p72/KHSRP results in a decrease of unloaded Ago2.
微小RNA（miRNA）是短链（21 - 23个核苷酸长）RNA，在植物和动物中通过转录后调控基因表达。它们是所有生物过程中的关键调节因子。在哺乳动物细胞中，miRNA被加载到AGO（精氨酸）蛋白家族的四个成员之一中，形成RNA诱导沉默复合体（RISC）。RISC抑制与其加载的miRNA具有序列互补性的mRNA的翻译。miRNA加工和miRNA介导的基因调控是高度受调控的过程，并且涉及许多RNA结合蛋白作为辅助因子。在这里，我们表明两种RNA结合蛋白p72和KHSRP，在促进miRNA生物合成中均具有已知作用，它们在转化的人类细胞中调节人类AGO2的蛋白质水平。我们确定p72和KHSRP通过调节细胞中的miRNA水平来影响AGO2的稳定性，并且p72 / KHSRP的缺失导致未加载的AGO2减少。
