Abstract
MicroRNAs (or miRNAs) are short nucleotide sequences (~17–22 bp long) that play important roles in gene regulation through targeting genes in the 3′untranslated regions (UTRs). Variants located in genomic regions might have different biological consequences in changing gene expression. Exonic variants (e.g., coding variant and 3′UTR variant) are often causative of diseases due to their influence on gene product. Variants harbored in the 3′UTR region where miRNAs perform their targeting function could potentially alter the binding relationships for target pairs, which could relate to disease causation. We gathered miRNA–mRNA targeting pairs from published studies and then employed the database of microRNA Target Site single nucleotide variants (SNVs) (dbMTS) to discover novel SNVs within the selected pairs. We identified a total of 183 SNVs for the 114 pairs of accurate miRNA–mRNA targeting pairs selected. Detailed bioinformatics analysis of the three genes with identified variants that were exclusively located in the 3′UTR section indicated their association with intellectual disability (ID). Our result showed an exceptionally high expression of GPR88 in brain tissues based on GTEx gene expression data, while WNT7A expression data were relatively high in brain tissues when compared to other tissues. Motif analysis for the 3′UTR region of WNT7A showed that five identified variants were well-conserved across three species (human, mouse, and rat); the motif that contains the variant identified in GPR88 is significant at the level of the 3′UTR of the human genome. Studies of pathways, protein–protein interactions, and relations to diseases further suggest potential association with intellectual disability of our discovered SNVs. Our results demonstrated that 3′UTR variants could change target interactions of miRNA–mRNA pairs in the context of their association with ID. We plan to automate the methods through developing a bioinformatics pipeline for identifying novel 3′UTR SNVs harbored by miRNA-targeted genes in the future.
Highlights
Intellectual disability (ID), called mental retardation (MR) or intellectual developmental disorder (IDD), is defined as a group of developmental conditions characterized by significant impairment of cognitive functions which are associated with limitations of learning, adaptive behavior, and skills [1]
Existing literatures have reported miRNAs and their target genes associated with intellectual disability (ID), but genetic variants located in the 30 untranslated regions (UTRs) region have not been elucidated for the target relationship creation and/or disruption
Using dbMTS, we discovered novel variants in the 30 UTR of genes associated with intellectual disability and targeted by miRNAs
Summary
Intellectual disability (ID), called mental retardation (MR) or intellectual developmental disorder (IDD), is defined as a group of developmental conditions characterized by significant impairment of cognitive functions which are associated with limitations of learning, adaptive behavior, and skills [1]. It requires the following criteria for a characterization of ID: (1) deficits in intellectual functioning—“reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience”—confirmed by clinical evaluation and individualized standard IQ testing; (2) deficits in adaptive functioning that significantly hamper conforming to developmental and. Previous studies have found that Fragile X Syndrome, another kind of ID, is caused by the absence of the Fragile X Mental
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.
