Alteration of processing induced by a single nucleotide polymorphism in pri-miR-126.

Alteration of processing induced by a single nucleotide polymorphism in pri-miR-126.
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DOI:
10.1016/j.bbrc.2010.07.009
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发表时间:
2010-08-20
影响因子:
3.1
通讯作者:
Kotani, Ai
Kotani, Ai
中科院分区:
生物学4区
文献类型:
--
作者:
Harnprasopwat, Ratanakanit;Ha, Daon;Toyoshima, Takae;Lodish, Harvey;Tojo, Arinobu;Kotani, Ai

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MicroRNAs(MiRNAs)是一种小的非编码RNA,在转录后水平抑制特定靶基因的表达。MiRNA基因的序列变异,包括pri-miRNAs、Pre-miRNAs和成熟miRNAs,可能会潜在地影响miRNAs的加工和/或靶标选择。在本研究中,我们在来自MLL-AF4 ALL患者的RS4;11细胞基因组中发现了成熟miR-126基因第24位核苷酸(+24)的单核苷酸多态性(SNP)。通过一系列体内分析,我们发现这种miR-126 SNP显著阻止了pri-miRNA向成熟miRNA的加工,并减少了miRNA介导的翻译抑制。而且,它的频率在不同种族之间是不同的。因此,我们的研究强调了发现新的miRNA SNP及其对miRNA生物发生的贡献的重要性,miRNA生物发生可能与人类遗传病有关。
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 found the single nucleotide polymorphism (SNP) at the twenty-fourth nucleotide (+24) of the mature miR-126 in the genome of RS4;11 cells, derived from a MLL-AF4 ALL patient. Through a series of in vivo analyzes, we found that this miR-126 SNP significantly blocks the processing of pri-miRNA to mature miRNA, as well as reduces miRNA-mediated translational suppression. Moreover, its frequency is different among races. Thus, our study emphasizes the importance of identifying new miRNA SNP and its contribution to miRNA biogenesis which is possible link to human genetic disease.
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