Survival of motor neuron

Function

The SMN protein contains GEMIN2-binding, Tudor and YG-Box domains. It localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as GEMIN2 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein.

SMN complex

SMN complex refers to the entire multi-protein complex involved in the assembly of snRNPs, the essential components of spliceosomal machinery. The complex, apart from the "proper" survival of motor neuron protein, includes at least six other proteins (gem-associated protein 2, 3, 4, 5, 6 and 7.

Interactions

SMN has been shown to interact with:

• Bcl-2,
• Coilin,
• DDX20,
• DHX9,
• FBL,
• FUBP1,
• GAR1,
• GEMIN2,
• GEMIN4,
• GEMIN5,
• GEMIN7,
• HNRNPR,
• KPNB1,
• P53,
• SNRPD1, and
• SNRPD2.

Evolutionary conservation

SMN is evolutionarily conserved including the Fungi kingdom, though only fungal organisms with a great number of introns have the Smn gene (or the splicing factor spf30 paralogue). Surprisingly, these are filamentous fungus which have mycelia, so suggesting analogy to the neuronal axons.

References

References

1. (January 2001). "SMN tudor domain structure and its interaction with the Sm proteins". Nature Structural Biology.
2. "Expasy - ProtParam".
3. (2009). "A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy". RNA Biology.
4. (March 2006). "Neuronal-specific roles of the survival motor neuron protein: evidence from survival motor neuron expression patterns in the developing human central nervous system". Journal of Neuropathology and Experimental Neurology.
5. (November 2012). "The survival motor neuron protein forms soluble glycine zipper oligomers". Structure.
6. "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
7. (May 2004). "The SMN complex". Experimental Cell Research.
8. (November 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature.
9. (September 2002). "Coilin methylation regulates nuclear body formation". Developmental Cell.
10. (October 2001). "Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein". Genes & Development.
11. (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes & Development.
12. (December 1999). "Gemin3: A novel DEAD box protein that interacts with SMN, the spinal muscular atrophy gene product, and is a component of gems". The Journal of Cell Biology.
13. (January 2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". The Journal of Cell Biology.
14. (July 2001). "The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1". Current Biology.
15. (March 2000). "The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain". FEBS Letters.
16. (August 2000). "Characterization of a nuclear 20S complex containing the survival of motor neurons (SMN) protein and a specific subset of spliceosomal Sm proteins". Human Molecular Genetics.
17. (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". The Journal of Biological Chemistry.
18. (August 2002). "Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex". The Journal of Biological Chemistry.
19. (March 2002). "Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component". The Journal of Biological Chemistry.
20. (October 2001). "SMN interacts with a novel family of hnRNP and spliceosomal proteins". The EMBO Journal.
21. (January 2002). "Specific interaction of Smn, the spinal muscular atrophy determining gene product, with hnRNP-R and gry-rbp/hnRNP-Q: a role for Smn in RNA processing in motor axons?". Human Molecular Genetics.
22. (July 2002). "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta". Human Molecular Genetics.
23. (January 2002). "A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy". The Journal of Biological Chemistry.
24. (January 2012). "Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy". Gene.