TranSNPs: A class of functional SNPs affecting mRNA translation potential revealed by fraction-based allelic imbalance

Autor: Samuel Valentini, Caterina Marchioretti, Alessandra Bisio, Annalisa Rossi, Sara Zaccara, Alessandro Romanel, Alberto Inga
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 12, Pp 103531- (2021)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.103531
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.
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