MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation

MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation
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DOI:
10.1016/j.molcel.2008.05.001
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发表时间:
2008-05-23
期刊:
影响因子:
16
通讯作者:
Lund, Anders H.
Lund, Anders H.
中科院分区:
生物学1区
文献类型:
--
作者:
Orom, Ulf Andersson;Nielsen, Finn Cilius;Lund, Anders H.

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MicroRNA(miRNAs)是一类小分子RNA,在基因表达中起转录后调节作用。miRNA影响多种信号通路,并且受损的miRNA调节可能有助于癌症和其他疾病的发展。在这里,我们表明,miRNA miR-10a与编码核糖体蛋白的mRNA的5'非翻译区相互作用,以增强其翻译。miR-10a缓解了氨基酸饥饿期间核糖体蛋白mRNA的翻译抑制,并且是茴香霉素处理或RAS过表达后其翻译诱导所必需的。我们发现miR-10a直接结合在调控57013基序的下游,并且57013调控复合物和miR-10a在功能上相互连接。结果表明,miR-10 a可能通过刺激核糖体蛋白mRNA翻译和核糖体生物合成来积极控制整体蛋白质合成,从而影响细胞进行转化的能力。
MicroRNAs (miRNAs) are small RNAs that function as posttranscriptional regulators of gene expression. miRNAs affect a variety of signaling pathways, and impaired miRNA regulation may contribute to the development of cancer and other diseases. Here we show that miRNA miR-10a interacts with the 5' untranslated region of mRNAs encoding ribosomal proteins to enhance their translation. miR-10a alleviates translational repression of the ribosomal protein mRNAs during amino acid starvation and is required for their translational induction following anisomycin treatment or overexpression of RAS. We show that miR-10a binds immediately downstream of the regulatory 57013 motif and that the 57013 regulatory complex and miR-10a are functionally interconnected. The results show that miR-10a may positively control global protein synthesis via the stimulation of ribosomal protein mRNA translation and ribosome biogenesis and hereby affect the ability of cells to undergo transformation.