PT - JOURNAL ARTICLE AU - Binda, Olivier AU - Juillard, Franceline AU - Ducassou, Julia Novion AU - Kleijwegt, Constance AU - Paris, Geneviève AU - Didillon, Andréanne AU - Baklouti, Faouzi AU - Corpet, Armelle AU - Couté, Yohann AU - Côté, Jocelyn AU - Lomonte, Patrick TI - SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members AID - 10.26508/lsa.202201429 DP - 2023 Jan 01 TA - Life Science Alliance PG - e202201429 VI - 6 IP - 1 4099 - https://www.life-science-alliance.org/content/6/1/e202201429.short 4100 - https://www.life-science-alliance.org/content/6/1/e202201429.full SO - Life Sci. Alliance2023 Jan 01; 6 AB - 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 (FMRFM). Importantly, SMA-linked SMNTUDOR mutant forms (SMNST) failed to interact with FMRFM. In agreement with the recent work, we define biochemically that SMN forms droplets in vitro and these droplets are stabilized by RNA, suggesting that SMN could be involved in the formation of membraneless organelles, such as Cajal nuclear bodies. Finally, we found that SMN and FMRP co-fractionate with polysomes, in an RNA-dependent manner, suggesting a potential role in localized translation in motor neurons.