Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA
Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA
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DOI：
10.1093/hmg/ddm062
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发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Jin, Peng
中科院分区：
文献类型：
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作者：
Duan, Ranhui;Pak, ChangHui;Jin, Peng
microRNA（miRNAs）是一类在转录后水平抑制特定靶基因表达的小分子非编码RNA。miRNA基因（包括pri-miRNAs、pre-miRNAs和成熟miRNAs）中的序列变异可能潜在地影响miRNAs的加工和/或靶标选择。在这项研究中，我们系统地鉴定了与227种已知人类miRNAs相关的单核苷酸多态性（SNP）。在我们鉴定的323个SNPs中，12个位于miRNA前体中，一个位于成熟miR-125 a的第八个核苷酸（+8），这被认为在miRNA识别mRNA靶点中起关键作用。通过一系列的体内分析，我们意外地发现这种miR-125 a SNP除了减少miRNA介导的翻译抑制外，还显著阻断pri-miRNA向pre-miRNA的加工。因此，我们的研究揭示了pri-miRNA加工的额外结构要求，并强调了鉴定新的miRNA SNP及其对miRNA生物发生和人类遗传疾病的贡献的重要性。
MicroRNAs (miRNAs) are small non-coding RNAs that inhibit expression of specific target genes at the post-transcriptional level. Sequence variations in miRNA genes, including pri-miRNAs, pre-miRNAs and mature miRNAs, could potentially influence the processing and/or target selection of miRNAs. In this study, we have systematically identified single nucleotide polymorphisms (SNPs) associated with 227 known human miRNAs. Among 323 total SNPs that we identify, 12 are located within the miRNA precursor and one is at the eighth nucleotide (+8) of the mature miR-125a, which has been proposed to play a critical role in recognition of mRNA targets by miRNAs. Through a series of in vivo analyses, we unexpectedly find that this miR-125a SNP significantly blocks the processing of pri-miRNA to pre-miRNA, in addition to reducing miRNA-mediated translational suppression. Thus, our study reveals an additional structural requirement for pri-miRNA processing and emphasizes the importance of identifying new miRNA SNPs and their contributions to miRNA biogenesis and human genetic disease.