A somatic mutation in the 5′UTR of BRCA1 gene in sporadic breast cancer causes down-modulation of translation efficiency

摘要: Mutations in the 5' UTR which cause increment/decrement of translation efficiency have been recently described as a novel molecular mechanism disease. Alterations consensus sequence for initiation may promote context-dependent leaky scanning ribosomes and/or from downstream AUG codon. Initiation in-frame codon BRCA1 gene was identified normal cells and possibly breast cancer. Here we present further insight into translational pathophysiology investigating role canonical structure BRCA1. We analysed effect somatic point mutation (117 G>C) position -3 with respect to gene, highly aggressive sporadic constructed chimeric genes encoding luciferase reporter wild type or mutated 5'UTR. These transcripts were tested their activity vitro vivo systems. In transcription/translation assays estimated construct 5'UTR 30-50% lower than that The same expression by transient transfection human cells. While two constructs equally transcribed, plasmid carrying produced 70% less compared sequence. Finally, obtain direct evaluation on vivo, mRNA translationally active non-active separated transfected Mutant partially localized subpolysomal particles analytically confirming polysome recruitment defect. Thus, characterization seems provide new ovarian cancer pathogenesis.