Survival of motor neuron

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Survival motor neuron protein
Protein SMN1 PDB 1g5v.png
Tudor domain from human SMN. PDB 1g5v [1]
Identifiers
SymbolSMN
Pfam PF06003
Pfam clan CL0049
InterPro IPR010304
SCOP2 1mhn / SCOPe / SUPFAM

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

Contents

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:

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. [26]

See also

Related Research Articles

snRNPs, or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pre-mRNA occurs. The action of snRNPs is essential to the removal of introns from pre-mRNA, a critical aspect of post-transcriptional modification of RNA, occurring only in the nucleus of eukaryotic cells. Additionally, U7 snRNP is not involved in splicing at all, as U7 snRNP is responsible for processing the 3′ stem-loop of histone pre-mRNA.

Small nuclear RNA (snRNA) is a class of small RNA molecules that are found within the splicing speckles and Cajal bodies of the cell nucleus in eukaryotic cells. The length of an average snRNA is approximately 150 nucleotides. They are transcribed by either RNA polymerase II or RNA polymerase III. Their primary function is in the processing of pre-messenger RNA (hnRNA) in the nucleus. They have also been shown to aid in the regulation of transcription factors or RNA polymerase II, and maintaining the telomeres.

Gideon Dreyfuss is an American biochemist who is the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.

<i>SMN1</i>

Survival of motor neuron 1 (SMN1), also known as component of gems 1 or GEMIN1, is a gene that encodes the SMN protein in humans.

Small nuclear ribonucleoprotein D1

Small nuclear ribonucleoprotein Sm D1 is a protein that in humans is encoded by the SNRPD1 gene.

SNRPB

Small nuclear ribonucleoprotein-associated proteins B and B' is a protein that in humans is encoded by the SNRPB gene.

Small nuclear ribonucleoprotein D2

Small nuclear ribonucleoprotein Sm D2 is a protein that in humans is encoded by the SNRPD2 gene. It belongs to the small nuclear ribonucleoprotein core protein family, and is required for pre-mRNA splicing and small nuclear ribonucleoprotein biogenesis. Alternative splicing occurs at this locus and two transcript variants encoding the same protein have been identified.

Small nuclear ribonucleoprotein polypeptide E

Small nuclear ribonucleoprotein E is a protein that in humans is encoded by the SNRPE gene.

SNRPD3

Small nuclear ribonucleoprotein Sm D3 is a protein that in humans is encoded by the SNRPD3 gene.

Gem-associated protein 2

Gem-associated protein 2 (GEMIN2), also called survival of motor neuron protein-interacting protein 1 (SIP1), is a protein that in humans is encoded by the GEMIN2 gene.

DDX20

Probable ATP-dependent RNA helicase DDX20, also known as DEAD-box helicase 20 and gem-associated protein 3 (GEMIN3), is an enzyme that in humans is encoded by the DDX20 gene.

Small nuclear ribonucleoprotein polypeptide F

Small nuclear ribonucleoprotein F is a protein that in humans is encoded by the SNRPF gene.

SNRPB2

U2 small nuclear ribonucleoprotein B is a protein that in humans is encoded by the SNRPB2 gene.

SNRPG

Small nuclear ribonucleoprotein G is a protein that in humans is encoded by the SNRPG gene.

Small nuclear ribonucleoprotein polypeptide C

U1 small nuclear ribonucleoprotein C is a protein that in humans is encoded by the SNRPC gene.

Gem-associated protein 6

Gem-associated protein 6 is a protein that in humans is encoded by the GEMIN6 gene. The gem-associated proteins are those found in the gems of Cajal bodies.

Gem-associated protein 4

Gem-associated protein 4 is a protein that in humans is encoded by the GEMIN4 gene.

Gem-associated protein 5

Gem-associated protein 5 is a protein that in humans is encoded by the GEMIN5 gene.

<i>SMN2</i>

Survival of motor neuron 2 (SMN2) is a gene that encodes the SMN protein in humans.

GEMIN8

Gem-associated protein 8 (Gemin-8) is a protein that in humans is encoded by the GEMIN8 gene.

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. 1 2 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. 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. 1 2 3 Carnegie GK, Sleeman JE, Morrice N, Hastie CJ, Peggie MW, Philp A, Lamond AI, Cohen PT (May 2003). "Protein phosphatase 4 interacts with the Survival of Motor Neurons complex and enhances the temporal localisation of snRNPs". Journal of Cell Science. 116 (Pt 10): 1905–13. doi: 10.1242/jcs.00409 . PMID   12668731.
  11. 1 2 3 4 5 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. 1 2 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. doi: 10.1016/S0960-9822(01)00316-5 . PMID   11509230.
  16. ↑ 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. doi:10.1016/S0014-5793(00)01320-X. PMID   10734235.
  17. 1 2 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.
  24. ↑ 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.
  25. ↑ 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.
  26. ↑ 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" (PDF). Gene. 491 (2): 135–41. doi:10.1016/j.gene.2011.10.006. PMID   22020225.
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