Loss-of-function variants in RNA binding motif protein X-linked induce neuronal defects contributing to amyotrophic lateral sclerosis pathogenesis.

ABSTRACT: Despite being one of the most prevalent RNA modifications, the role of N6-methyladenosine (m6A) in amyotrophic lateral sclerosis (ALS) remains ambiguous. In this investigation, we explore the contribution of genetic defects of m6A-related genes to ALS pathogenesis. We scrutinized the mutation landscape of m6A genes through a comprehensive analysis of whole-exome sequencing cohorts, encompassing 508 ALS patients and 1660 population-matched controls. Our findings reveal a noteworthy enrichment of RNA binding motif protein X-linked (RBMX) variants among ALS patients, with a significant correlation between pathogenic m6A variants and adverse clinical outcomes. Furthermore, Rbmx knockdown in NSC-34 cells overexpressing mutant TDP43^Q331K results in cell death mediated by

SUBMITTER: He D 

PROVIDER: S-EPMC11387721 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature