Short RNAs repress translation after initiation in mammalian cells
Short RNAs repress translation after initiation in mammalian cells
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DOI：
10.1016/j.molcel.2006.01.031
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发表时间：
2006-02-17
期刊：
影响因子：
16
通讯作者：
Sharp, PA
中科院分区：
文献类型：
--
作者：
Petersen, CP;Bordeleau, ME;Sharp, PA
MicroRNA (miRNA) 预计可通过与 3' 非翻译区 (UTR) 相互作用来调节 30% 的哺乳动物蛋白质编码基因。我们使用部分互补的 siRNA 来研究 miRNA 介导人类细胞翻译抑制的机制。被抑制的 mRNA 与参与翻译延伸的多核糖体相关，如嘌呤霉素敏感性所示。这种抑制似乎发生在起始后，因为 HCV IRES 和 CrPV IRES 的帽独立过程驱动的翻译受到短 RNA 的抑制。此外，代谢标记表明沉默发生在新生多肽链完成之前。此外，短RNA的沉默会导致终止密码子处的翻译通读减少，并且在翻译起始阻断后，受抑制的mRNA上的核糖体比对照mRNA上的核糖体解离得更快。这些结果表明，短 RNA 以及可能的 miRNA 的抑制主要是由于翻译延伸过程中核糖体的脱落。
MicroRNAs (miRNAs) are predicted to regulate 30% of mammalian protein-encoding genes by interactions with their 3' untranslated regions (UTRs). We use partially complementary siRNAs to investigate the mechanism by which miRNAs mediate translational repression in human cells. Repressed mRNAs are associated with polyribosomes that are engaged in translation elongation, as shown by puromycin sensitivity. The inhibition appears to be postinitiation because translation driven by the cap-independent processes of HCV IRES and CrPV IRES is repressed by short RNAs. Further, metabolic labeling suggests that silencing occurs before completion of the nascent polypeptide chain. In addition, silencing by short RNAs causes a decrease in translational readthrough at a stop codon, and ribosomes on repressed mRNAs dissociate more rapidly after a block of initiation of translation than those on control mRNAs. These results suggest that repression by short RNAs, and thus probably miRNAs, is primarily due to ribosome drop off during elongation of translation.