RT Journal Article
SR Electronic
T1 SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201429
DO 10.26508/lsa.202201429
VO 6
IS 1
A1 Binda, Olivier
A1 Juillard, Franceline
A1 Ducassou, Julia Novion
A1 Kleijwegt, Constance
A1 Paris, Geneviève
A1 Didillon, Andréanne
A1 Baklouti, Faouzi
A1 Corpet, Armelle
A1 Couté, Yohann
A1 Côté, Jocelyn
A1 Lomonte, Patrick
YR 2023
UL https://www.life-science-alliance.org/content/6/1/e202201429.abstract
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.