Abstract
BackgroundMicroRNAs (miRNAs) are important genetic elements that regulate the expression of thousands of human genes. Polymorphisms affecting miRNA biogenesis, dosage and target recognition may represent potentially functional variants. The functional consequences of single nucleotide polymorphisms (SNPs) within critical miRNA sequences and outside of miRNA genes were previously demonstrated using both experimental and computational methods. However, little is known about how copy number variations (CNVs) affect miRNA genes.ResultsIn this study, we analyzed the co-localization of all miRNA loci with known CNV regions. Using bioinformatic tools we identified and validated 209 copy number variable miRNA genes (CNV-miRNAs) in CNV regions deposited in Database of Genomic Variations (DGV) and 11 CNV-miRNAs in two sets of CNVs defined as highly polymorphic. We propose potential mechanisms of CNV-mediated variation of functional copies of miRNAs (dosage) for different types of CNVs overlapping miRNA genes. We also showed that, consistent with their essential biological functions, miRNA loci are underrepresented in highly polymorphic and well-validated CNV regions.ConclusionWe postulate that CNV-miRNAs are potential functional variants and should be considered high priority candidate variants in genotype-phenotype association studies.
Highlights
MicroRNAs are important genetic elements that regulate the expression of thousands of human genes
By comparing fractions of miRNAs and the genome that are covered by differentially validated copy number variations (CNVs) regions, we showed that miRNA loci are underrepresented in highly polymorphic CNVs, but not in CNVs deposited in the Database of Genomic Variations (DGV) database
Since the exact boundaries of miRNA genes are difficult to determine, we used the genomic coordinates of all pre-miRNA loci deposited in miRBase (v 13.0; N = 715) as a proxy of miRNA gene sequences [33,34]
Summary
MicroRNAs (miRNAs) are important genetic elements that regulate the expression of thousands of human genes. Polymorphisms affecting miRNA biogenesis, dosage and target recognition may represent potentially functional variants. The functional consequences of single nucleotide polymorphisms (SNPs) within critical miRNA sequences and outside of miRNA genes were previously demonstrated using both experimental and computational methods. MicroRNAs (miRNAs) are a family of short (~20 nt), single-stranded, noncoding RNAs that are primarily involved in post-transcriptional down-regulation of gene expression in most eukaryotes [1]. Functional miRNAs are generated from primary precursors (pri-miRNA) encoded either by independent transcriptional units or within protein- or RNA-coding genes. Maturation of miRNAs involves two subsequent RNA cleavage steps. The pre-miRNAs (~60 nt) possess a hairpin structure, with the double-stranded portion interrupted by one or more mismatched nucleotides. The miRNA-induced silencing complex (miRISC) interacts with complementary target sequences, which are usually located within the 3’ untranslated regions (3’UTRs) of mRNAs, causing mRNA degradation or inhibition of translation [7,8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
