Article

SNPs in human miRNA genes affect biogenesis and function. Rna

Department of Molecular Biology, City of Hope National Medical Center, Duarte, California 91010, USA.
RNA (Impact Factor: 4.94). 08/2009; 15(9):1640-51. DOI: 10.1261/rna.1560209
Source: PubMed

ABSTRACT

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.

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    • "SNPs in the porcine miR-206/miR- 133b cluster have been found to be genetic factors affecting muscle and meat quality traits (Lee et al., 2013). These studies suggest a greater role of genomic variations in modulating miRNA function and regulation, manifesting as phenotypic correlates (Sun et al., 2009). "
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    • "Accepted April 27, 2015. 1 Corresponding author: tanja.kunej@bf.uni-lj.si within seed regions (mir-seed-SNP), would be expected to exhibit a complex biological effect (Sun et al., 2009). "
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    • "The variant was predicted to alter the secondary structure around the Drosha processing site . Functional validation showed that the variant results in increased expression of pre - miR - 510 , miR - 510 - 5p , and miR - 510 - 3p ( Feng et al . , 2009 ; Sun et al . , 2009 ) . A variant affecting Dicer processing is rs546098287 , located within the seed sequence of miR - 96 - 3p . This variant was identified as the causative mutation in an Italian family with non - syndromic hearing loss ( Soldà et al . , 2012 ) . Two segregating point mutations in miR - 96 - 5p were previously identified in two Spanish f"
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