SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members.

ABSTRACT: Although recent advances in gene therapy provide hope for spinal muscular atrophy (SMA) patients, the pathology remains the leading genetic cause of infant mortality. SMA is a monogenic pathology that originates from the loss of the SMN1 gene in most cases or mutations in rare cases. Interestingly, several SMN1 mutations occur within the TUDOR methylarginine reader domain of SMN. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a BioID proteomic approach, we have identified and validated a number of SMN-interacting proteins, including fragile X mental retardation protein (FMRP) family members (FMR_FM). Importantly, SMA-linked SMN_TUDOR mutant forms (SMN

SUBMITTER: Binda O 

PROVIDER: S-EPMC9684302 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature