Survival of motor neuron explained

Symbol:SMN
Survival motor neuron protein
Pfam:PF06003
Pfam Clan:CL0049
Interpro:IPR010304
Scop:1mhn

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

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.[1] 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.[2]

Function

The SMN protein contains GEMIN2-binding, Tudor and YG-Box domains.[3] 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.[4]

SMN complex

SMN complex refers to the entire multi-protein complex involved in the assembly of snRNPs, the essential components of spliceosomal machinery.[5] 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:

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.[24]

See also

Notes and References

  1. Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN . 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 . 2009 . 19430205 . 2734876 . 10.4161/rna.6.3.8723.
  2. Giavazzi A, Setola V, Simonati A, Battaglia G . 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 . March 2006 . 16651888 . 10.1097/01.jnen.0000205144.54457.a3 . free .
  3. Martin R, Gupta K, Ninan NS, Perry K, Van Duyne GD . The survival motor neuron protein forms soluble glycine zipper oligomers . Structure . 20 . 11 . 1929–39 . November 2012 . 23022347 . 3519385 . 10.1016/j.str.2012.08.024 .
  4. Web site: Entrez Gene: SMN1 survival of motor neuron 1, telomeric.
  5. Gubitz AK, Feng W, Dreyfuss G . The SMN complex . Experimental Cell Research . 296 . 1 . 51–6 . May 2004 . 15120993 . 10.1016/j.yexcr.2004.03.022 .
  6. Iwahashi H, Eguchi Y, Yasuhara N, Hanafusa T, Matsuzawa Y, Tsujimoto Y . Synergistic anti-apoptotic activity between Bcl-2 and SMN implicated in spinal muscular atrophy . Nature . 390 . 6658 . 413–7 . November 1997 . 9389483 . 10.1038/37144 . 1997Natur.390..413I .
  7. Hebert MD, Shpargel KB, Ospina JK, Tucker KE, Matera AG . Coilin methylation regulates nuclear body formation . Developmental Cell . 3 . 3 . 329–37 . September 2002 . 12361597 . 10.1016/S1534-5807(02)00222-8 . free .
  8. Hebert MD, Szymczyk PW, Shpargel KB, Matera AG . Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein . Genes & Development . 15 . 20 . 2720–9 . October 2001 . 11641277 . 312817 . 10.1101/gad.908401 .
  9. Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G . miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs . Genes & Development . 16 . 6 . 720–8 . March 2002 . 11914277 . 155365 . 10.1101/gad.974702 .
  10. Charroux B, Pellizzoni L, Perkinson RA, Shevchenko A, Mann M, Dreyfuss G . 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 . December 1999 . 10601333 . 2168095 . 10.1083/jcb.147.6.1181 .
  11. Pellizzoni L, Charroux B, Rappsilber J, Mann M, Dreyfuss G . A functional interaction between the survival motor neuron complex and RNA polymerase II . The Journal of Cell Biology . 152 . 1 . 75–85 . January 2001 . 11149922 . 2193649 . 10.1083/jcb.152.1.75 .
  12. Pellizzoni L, Baccon J, Charroux B, Dreyfuss G . The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1 . Current Biology . 11 . 14 . 1079–88 . July 2001 . 11509230 . 10.1016/S0960-9822(01)00316-5 . free . 2001CBio...11.1079P .
  13. Williams BY, Hamilton SL, Sarkar HK . The survival motor neuron protein interacts with the transactivator FUSE binding protein from human fetal brain . FEBS Letters . 470 . 2 . 207–10 . March 2000 . 10734235 . 10.1016/S0014-5793(00)01320-X . 2000FEBSL.470..207W .
  14. Liu Q, Fischer U, Wang F, Dreyfuss G . 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 . September 1997 . 9323129 . 10.1016/S0092-8674(00)80367-0 . free .
  15. Meister G, Bühler D, Laggerbauer B, Zobawa M, Lottspeich F, Fischer U . 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 . August 2000 . 10942426 . 10.1093/hmg/9.13.1977 . free .
  16. Gubitz AK, Mourelatos Z, Abel L, Rappsilber J, Mann M, Dreyfuss G . Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins . The Journal of Biological Chemistry . 277 . 7 . 5631–6 . February 2002 . 11714716 . 10.1074/jbc.M109448200 . free .
  17. Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G . Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex . The Journal of Biological Chemistry . 277 . 35 . 31957–62 . August 2002 . 12065586 . 10.1074/jbc.M203478200 . free .
  18. Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G . 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 . March 2002 . 11748230 . 10.1074/jbc.M110141200 . free .
  19. Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G . SMN interacts with a novel family of hnRNP and spliceosomal proteins . The EMBO Journal . 20 . 19 . 5443–52 . October 2001 . 11574476 . 125643 . 10.1093/emboj/20.19.5443 .
  20. Rossoll W, Kröning AK, Ohndorf UM, Steegborn C, Jablonka S, Sendtner M . 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 . January 2002 . 11773003 . 10.1093/hmg/11.1.93 . free .
  21. Narayanan U, Ospina JK, Frey MR, Hebert MD, Matera AG . SMN, the spinal muscular atrophy protein, forms a pre-import snRNP complex with snurportin1 and importin beta . Human Molecular Genetics . 11 . 15 . 1785–95 . July 2002 . 12095920 . 1630493 . 10.1093/hmg/11.15.1785 .
  22. Young PJ, Day PM, Zhou J, Androphy EJ, Morris GE, Lorson CL . 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 . January 2002 . 11704667 . 10.1074/jbc.M108769200 . free .
  23. Friesen WJ, Dreyfuss G . 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 . August 2000 . 10851237 . 10.1074/jbc.M003299200 . free .
  24. Mier P, Pérez-Pulido AJ . 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 . January 2012 . 22020225 . 10.1016/j.gene.2011.10.006 .

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