Survival of motor neuron

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

Survival motor neuron protein
Tudor domain from human SMN. PDB 1g5v[1]
Identifiers
Symbol	SMN
Pfam	PF06003
Pfam clan	CL0049
InterPro	IPR010304
SCOP2	1mhn / SCOPe / SUPFAM
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

SMN is found in the cytoplasm of all animal cells and also in the nuclear gems. It functions in transcriptional regulation, telomerase regeneration and cellular trafficking.^[2] SMN deficiency, primarily due to mutations in SMN1, results in widespread splicing defects, especially in spinal motor neurons, and is one cause of spinal muscular atrophy. Research also showed a possible role of SMN in neuronal migration and/or differentiation.^[3]

Function

The SMN protein contains GEMIN2-binding, Tudor and YG-Box domains.^[4] 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.^[5]

SMN complex

SMN complex refers to the entire multi-protein complex involved in the assembly of snRNPs, the essential components of spliceosomal machinery.^[6] 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.^[6]

Interactions

SMN has been shown to interact with:

• Bcl-2,^[7]
• Coilin,^[8][9]
• DDX20,^[10][11][12]
• DHX9,^[13]
• FBL,^[14]
• FUBP1,^[15]
• GAR1,^[14]
• GEMIN2,^[10][16]
• GEMIN4,^[10]
• GEMIN5,^[17]
• GEMIN7,^[18][19]
• HNRNPR,^[20][21]
• KPNB1,^[22]
• P53,^[23]
• SNRPD1,^[10][16][24] and
• SNRPD2.^[10]

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.^[25]

See also

• Gideon Dreyfuss

References

1. Selenko P, Sprangers R, Stier G, Bühler D, Fischer U, Sattler M (January 2001). "SMN tudor domain structure and its interaction with the Sm proteins". Nature Structural Biology. 8 (1): 27–31. doi:10.1038/83014. PMID 11135666.
2. Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN (2009). "A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy". RNA Biology. 6 (3): 341–50. doi:10.4161/rna.6.3.8723. PMC 2734876. PMID 19430205.
3. Giavazzi A, Setola V, Simonati A, Battaglia G (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. 65 (3): 267–77. doi:10.1097/01.jnen.0000205144.54457.a3. PMID 16651888.
4. Martin R, Gupta K, Ninan NS, Perry K, Van Duyne GD (November 2012). "The survival motor neuron protein forms soluble glycine zipper oligomers". Structure. 20 (11): 1929–39. doi:10.1016/j.str.2012.08.024. PMC 3519385. PMID 23022347.
5. "Entrez Gene: SMN1 survival of motor neuron 1, telomeric".
6. Gubitz AK, Feng W, Dreyfuss G (May 2004). "The SMN complex". Experimental Cell Research. 296 (1): 51–6. doi:10.1016/j.yexcr.2004.03.022. PMID 15120993.
7. Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y (November 1997). "Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy". Nature. 390 (6658): 413–7. Bibcode:1997Natur.390..413I. doi:10.1038/37144. PMID 9389483.
8. Hebert MD, Shpargel KB, Ospina JK, Tucker KE, Matera AG (September 2002). "Coilin methylation regulates nuclear body formation". Developmental Cell. 3 (3): 329–37. doi:10.1016/S1534-5807(02)00222-8. PMID 12361597.
9. Hebert MD, Szymczyk PW, Shpargel KB, Matera AG (October 2001). "Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein". Genes & Development. 15 (20): 2720–9. doi:10.1101/gad.908401. PMC 312817. PMID 11641277.
10. Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U (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. 9 (13): 1977–86. doi:10.1093/hmg/9.13.1977. PMID 10942426.
11. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G (March 2002). "miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs". Genes & Development. 16 (6): 720–8. doi:10.1101/gad.974702. PMC 155365. PMID 11914277.
12. Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G (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. 147 (6): 1181–94. doi:10.1083/jcb.147.6.1181. PMC 2168095. PMID 10601333.
13. Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G (January 2001). "A functional interaction between the survival motor neuron complex and RNA polymerase II". The Journal of Cell Biology. 152 (1): 75–85. doi:10.1083/jcb.152.1.75. PMC 2193649. PMID 11149922.
14. Pellizzoni L, Baccon J, Charroux B, Dreyfuss G (July 2001). "The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1". Current Biology. 11 (14): 1079–88. Bibcode:2001CBio...11.1079P. doi:10.1016/S0960-9822(01)00316-5. PMID 11509230.
15. Williams BY, Hamilton SL, Sarkar HK (March 2000). "The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain". FEBS Letters. 470 (2): 207–10. Bibcode:2000FEBSL.470..207W. doi:10.1016/S0014-5793(00)01320-X. PMID 10734235.
16. Liu Q, Fischer U, Wang F, Dreyfuss G (September 1997). "The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins". Cell. 90 (6): 1013–21. doi:10.1016/S0092-8674(00)80367-0. PMID 9323129.
17. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G (February 2002). "Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins". The Journal of Biological Chemistry. 277 (7): 5631–6. doi:10.1074/jbc.M109448200. PMID 11714716.
18. Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G (August 2002). "Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex". The Journal of Biological Chemistry. 277 (35): 31957–62. doi:10.1074/jbc.M203478200. PMID 12065586.
19. Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G (March 2002). "Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component". The Journal of Biological Chemistry. 277 (9): 7540–5. doi:10.1074/jbc.M110141200. PMID 11748230.
20. Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G (October 2001). "SMN interacts with a novel family of hnRNP and spliceosomal proteins". The EMBO Journal. 20 (19): 5443–52. doi:10.1093/emboj/20.19.5443. PMC 125643. PMID 11574476.
21. Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M (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. 11 (1): 93–105. doi:10.1093/hmg/11.1.93. PMID 11773003.
22. Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG (July 2002). "SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta". Human Molecular Genetics. 11 (15): 1785–95. doi:10.1093/hmg/11.15.1785. PMC 1630493. PMID 12095920.
23. Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL (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. 277 (4): 2852–9. doi:10.1074/jbc.M108769200. PMID 11704667.
24. Friesen WJ, Dreyfuss G (August 2000). "Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN)". The Journal of Biological Chemistry. 275 (34): 26370–5. doi:10.1074/jbc.M003299200. PMID 10851237.
25. Mier P, Pérez-Pulido AJ (January 2012). "Fungal Smn and Spf30 homologues are mainly present in filamentous fungi and genomes with many introns: implications for spinal muscular atrophy". Gene. 491 (2): 135–41. doi:10.1016/j.gene.2011.10.006. PMID 22020225.

External links

• SMN+protein+(spinal+muscular+atrophy) at the U.S. National Library of Medicine Medical Subject Headings (MeSH)