Inhibition of translational initiation by Let-7 microRNA in human cells
Inhibition of translational initiation by Let-7 microRNA in human cells
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DOI：
10.1126/science.1115079
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发表时间：
2005-09-02
期刊：
影响因子：
56.9
通讯作者：
Filipowicz, W
中科院分区：
文献类型：
--
作者：
Pillai, RS;Bhattacharyya, SN;Filipowicz, W
MicroRNA (miRNA) 类似于调节多细胞真核生物中基因表达的 21 个核苷酸长的 RNA 分子。在后生动物中，miRNA 通过与目标信使 RNA (mRNA) 的 3' 非翻译区不完美的碱基配对发挥作用，并通过未知机制抑制蛋白质积累。我们证明，内源性 let-7 微核糖核蛋白 (miRNP) 或 Argonaute (Ago) 蛋白与人类细胞中报告基因 mRNA 的束缚会抑制翻译起始。 M(7)G-cap 独立翻译不受抑制，表明 miRNP 干扰对 cap 的识别。研究发现，受抑制的 mRNA、Ago 蛋白和 miRNA 都会在加工体中积累。我们认为 mRNA 定位到这些结构是翻译抑制的结果。
MicroRNAs (miRNAs) are similar to 21-nucteotide-long RNA molecules regulating gene expression in multicellular eukaryotes. In metazoa, miRNAs act by imperfectly base-pairing with the 3' untranslated region of target messenger RNAs (mRNAs) and repressing protein accumulation by an unknown mechanism. We demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit translation initiation. M(7)G-cap-independent translation is not subject to repression, suggesting that miRNPs interfere with recognition of the cap. Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression.