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Human Molecular Genetics Advance Access originally published online on March 30, 2007
Human Molecular Genetics 2007 16(9):1124-1131; doi:10.1093/hmg/ddm062
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Ranhui Duan1, ChangHui Pak1,2 and Peng Jin1,2,*

1 Department of Human Genetics and 2 Graduate Program in Genetics and Molecular Biology, Emory University School of Medicine, Atlanta, GA 30322, USA

* To whom correspondence should be addressed at: Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, GA 30322, USA. Tel: +1 4047273729; Fax: +1 4047275408; Email: pjin{at}genetics.emory.edu

Received January 25, 2007; Accepted March 13, 2007

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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