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Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability

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 varian...

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Autores principales: Yang, Junmeng, Liu, Anna, He, Isabella, Bai, Yongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563394/
https://www.ncbi.nlm.nih.gov/pubmed/32858868
http://dx.doi.org/10.3390/genes11090998
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author Yang, Junmeng
Liu, Anna
He, Isabella
Bai, Yongsheng
author_facet Yang, Junmeng
Liu, Anna
He, Isabella
Bai, Yongsheng
author_sort Yang, Junmeng
collection PubMed
description 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.
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spelling pubmed-75633942020-10-27 Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability Yang, Junmeng Liu, Anna He, Isabella Bai, Yongsheng Genes (Basel) Article 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. MDPI 2020-08-26 /pmc/articles/PMC7563394/ /pubmed/32858868 http://dx.doi.org/10.3390/genes11090998 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Junmeng
Liu, Anna
He, Isabella
Bai, Yongsheng
Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title_full Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title_fullStr Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title_full_unstemmed Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title_short Bioinformatics Analysis Revealed Novel 3′UTR Variants Associated with Intellectual Disability
title_sort bioinformatics analysis revealed novel 3′utr variants associated with intellectual disability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563394/
https://www.ncbi.nlm.nih.gov/pubmed/32858868
http://dx.doi.org/10.3390/genes11090998
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