title: Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA.
abstract: 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.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.forename: Changhui
authors.initials: C
authors.lastname: Pak
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide; D014176:Protein Biosynthesis; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs; D012322:RNA Precursors