Mass spectrometry-based proteomic comparison of BirA-SMN, BirA-SMN-Y109C and BirA proxisomes.

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, SMN1 mutations occur broadly either within the TUDOR methyl-arginine (Rme) reader domain of SMN or its carboxy terminal oligomerization domain. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a proximity-dependent biotinylation proteomic (BioID) approach, we have identified and validated a number of SMN-interacting proteins, including Fragile X mental retardation family members (FMRFM), such as FMRP itself as well as FXR1 and FXR2, some depending on a wild-type version of the TUDOR domain.