Extensive post-transcriptional regulation of microRNAs and its implications for cancer
Extensive post-transcriptional regulation of microRNAs and its implications for cancer
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DOI：
10.1101/gad.1444406
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发表时间：
2006-08-15
影响因子：
10.5
通讯作者：
Hammond, Scott M.
中科院分区：
文献类型：
--
作者：
Thomson, J. Michael;Newman, Martin;Hammond, Scott M.
MicroRNA (miRNA) 是短的非编码 RNA，可在转录后调节基因表达。虽然数百个哺乳动物 miRNA 基因已被识别，但人们对调节活性 miRNA 种类产生的途径知之甚少。在这里，我们表明大部分 miRNA 基因受到转录后调控。在小鼠早期发育过程中，许多 miRNA 初级转录物（包括 Let-7 家族）以高水平存在，但不被酶 Drosha 加工。对原发性肿瘤中基因表达的分析表明，在癌症中观察到的 miRNA 广泛下调是由于 Drosha 处理步骤的失败。这些数据揭示了 miRNA 功能的一个新的调控步骤，并提供了癌症中 miRNA 下调的机制。
MicroRNAs (miRNAs) are short, noncoding RNAs that post-transcriptionally regulate gene expression. While hundreds of mammalian miRNA genes have been identified, little is known about the pathways that regulate the production of active miRNA species. Here we show that a large fraction of miRNA genes are regulated post-transcriptionally. During early mouse development, many miRNA primary transcripts, including the Let-7 family, are present at high levels but are not processed by the enzyme Drosha. An analysis of gene expression in primary tumors indicates that the widespread down-regulation of miRNAs observed in cancer is due to a failure at the Drosha processing step. These data uncover a novel regulatory step in miRNA function and provide a mechanism for miRNA down-regulation in cancer.