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

被引:44
|
作者
Harnprasopwat, Ratanakanit
Ha, Daon [2 ]
Toyoshima, Takae
Lodish, Harvey [3 ]
Tojo, Arinobu [4 ]
Kotani, Ai [1 ,4 ]
机构
[1] Univ Tokyo, Div Mol Therapy, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan
[2] Tuft Univ, Sch Med, Dept Med, Boston, MA USA
[3] MIT, Dept Biol, Cambridge, MA 02139 USA
[4] Univ Tokyo, Inst Med Sci, Dept Hematol & Oncol, Tokyo 1088639, Japan
基金
日本学术振兴会; 美国国家卫生研究院;
关键词
miRNA; SNP; Drosha; Processing; CHRONIC LYMPHOCYTIC-LEUKEMIA; DROSHA-DGCR8; COMPLEX; MESSENGER-RNA; HUMAN CANCER; MICRORNAS; EXPRESSION; MIRNAS; MICROARRAY; SUPPRESSOR; MIR-126;
D O I
10.1016/j.bbrc.2010.07.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-rniRNAs, 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. (c) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:117 / 122
页数:6
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