Unproductive alternative splicing of ATM exon 7: mapping of critical regulatory elements and identification of 34 spliceogenic variants.

ABSTRACT: ATM loss-of-function variants are significantly associated with increased breast cancer risk. ATM exon 7 skipping (△(E7)) is a naturally-occurring alternative splicing event, which introduces a premature termination codon and represents a form of gene-expression regulation via unproductive splicing. Disruption of splicing regulatory elements (SRE) by variants can lead to mis-splicing, potentially contributing to disease susceptibility. To study the regulatory mechanisms of △(E7) and the impact of exonic variants on splicing, a combined in silico/minigene approach was employed, using the construct mgATM_4-9 (exons 4-9) that recapitulates this splicing event. HEXplorer analysis of ATM exon 7 predicted two splicing enhancer-rich regions (c.665-681 and c.867-898). Deletions of these intervals

SUBMITTER: Llinares-Burguet I 

PROVIDER: S-EPMC12675606 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature