Spinal Muscular Atrophy (SMA) is a common, devastating and often fatal motor neuron degenerative disease. SMA results from reduced levels of, or mutations in, the SMN (survival of motor neurons) protein. Work on the molecular characterization of the SMN protein led to the discovery of several of its functions, revealing novel cellular pathways and proteins. The investigators found that SMN is part of a complex that contains several proteins. All the components of the complex are novel proteins and they have already characterized several of them. Because they are tightly associated with SMN, the other proteins of the complex must be considered to be collaborators or modifiers of SMN function, and thus play a role in the course and severity of SMA. They also are candidate disease genes for other neuronal diseases. The SMN complex is expressed in all cells, but particularly high levels are found in neurons. It is present in both the cytoplasm and in the nucleus where it is concentrated in nuclear bodies, they termed gems. SMN functions in the biogenesis of snRNPs, the essential building blocks of the pre-mRNA splicing machinery, and in the pre-mRNA splicing process itself. Much remains to be learned about the structure, functions, and mechanism of action of SMN and the SMN complex. Studies will be carried out to understand in details the molecular functions and interactions of the SMN protein and of the SMN complex. From these studies approaches to therapy of SMA are likely to emerge.
| Gubitz, Amelie K; Mourelatos, Zissimos; Abel, Linda et al. (2002) Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J Biol Chem 277:5631-6 |
| Wang, J; Dreyfuss, G (2001) Characterization of functional domains of the SMN protein in vivo. J Biol Chem 276:45387-93 |
