Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA | Zendy

Ranhui Duan | Zendy; ChangHui Pak | Zendy; Peng Jin | Zendy

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Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA

Author(s) -

Ranhui Duan,

ChangHui Pak,

Peng Jin

Publication year - 2007

Publication title -

human molecular genetics

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.811

H-Index - 276

eISSN - 1460-2083

pISSN - 0964-6906

DOI - 10.1093/hmg/ddm062

Subject(s) - biology , microrna , single nucleotide polymorphism , genetics , gene , gene silencing , gene expression , computational biology , genotype

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.

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