TranSNPs: A class of functional SNPs affecting mRNA translation potential revealed by fraction-based allelic imbalance
| Autor: | Alberto Inga, Caterina Marchioretti, Alessandra Bisio, Alessandro Romanel, Samuel Valentini, Annalisa Rossi, Sara Zaccara |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | iScience, Vol 24, Iss 12, Pp 103531-(2021) iScience |
| ISSN: | 2589-0042 |
| Popis: | Summary Few studies have explored the association between SNPs and alterations in mRNA translation potential. We developed an approach to identify SNPs that can mark allele-specific protein expression levels and could represent sources of inter-individual variation in disease risk. Using MCF7 cells under different treatments, we performed polysomal profiling followed by RNA sequencing of total or polysome-associated mRNA fractions and designed a computational approach to identify SNPs showing a significant change in the allelic balance between total and polysomal mRNA fractions. We identified 147 SNPs, 39 of which located in UTRs. Allele-specific differences at the translation level were confirmed in transfected MCF7 cells by reporter assays. Exploiting breast cancer data from TCGA we identified UTR SNPs demonstrating distinct prognosis features and altering binding sites of RNA-binding proteins. Our approach produced a catalog of tranSNPs, a class of functional SNPs associated with allele-specific translation and potentially endowed with prognostic value for disease risk. Graphical abstract Highlights • SNPs can alter mRNA translation potential • Polysomal imbalance of heterozygous SNPs can mark allele-specific protein expression • UTR SNPs associated with allele-specific translation demonstrate prognostic value Molecular mechanism of gene regulation; Computational bioinformatics; Transcriptomics |
| Databáze: | OpenAIRE |
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