SNPs in human miRNA genes affect biogenesis and function.
MicroRNAs (miRNAs) are 21-25-nucleotide-long, noncoding RNAs that are involved in translational regulation. Most miRNAs derive from a two-step sequential processing: the generation of pre-miRNA from pri-miRNA by the Drosha/DGCR8 complex in the nucleus, and the generation of mature miRNAs from pre-miRNAs by the Dicer/TRBP complex in the cytoplasm. Sequence variation around the processing sites, and sequence variations in the mature miRNA, especially the seed sequence, may have profound affects on miRNA biogenesis and function. In the context of analyzing the roles of miRNAs in Schizophrenia and Autism, we defined at least 24 human X-linked miRNA variants. Functional assays were developed and performed on these variants. In this study we investigate the affects of single nucleotide polymorphisms (SNPs) on the generation of mature miRNAs and their function, and report that naturally occurring SNPs can impair or enhance miRNA processing as well as alter the sites of processing. Since miRNAs are small functional units, single base changes in both the precursor elements as well as the mature miRNA sequence may drive the evolution of new microRNAs by altering their biological function. Finally, the miRNAs examined in this study are X-linked, suggesting that the mutant alleles could be determinants in the etiology of diseases.
Sun
Guihua
G
Department of Molecular Biology, City of Hope National Medical Center, Duarte, California 91010, USA.
Yan
Jin
J
Noltner
Katie
K
Feng
Jinong
J
Li
Haitang
H
Sarkis
Daniel A
DA
Sommer
Steve S
SS
Rossi
John J
JJ
D001321:Autistic Disorder / Q000235:genetics; D001483:Base Sequence; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D050172:Genes, X-Linked / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D009690:Nucleic Acid Conformation; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D035683:MicroRNAs; D022821:RNA Splice Sites