ALS-linked TDP-43 mutations interfere with the recruitment of RNA recognition motifs to G-quadruplex RNA.

ABSTRACT: TDP-43 is a major pathological protein in sporadic and familial amyotrophic lateral sclerosis (ALS) and mediates mRNA fate. TDP-43 dysfunction leads to causes progressive degeneration of motor neurons, the details of which remain elusive. Elucidation of the molecular mechanisms of RNA binding could enhance our understanding of this devastating disease. We observed the involvement of the glycine-rich (GR) region of TDP-43 in the initial recognition and binding of G-quadruplex (G4)-RNA in conjunction with its RNA recognition motifs (RRM). We performed a molecular dissection of these intramolecular RNA-binding modules in this study. We confirmed that the ALS-linked mutations in the GR region lead to alteration in the G4 structure. In contrast, amino acid substitutions in the GR region alter t

SUBMITTER: Ishiguro A 

PROVIDER: S-EPMC10097714 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature