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Gene Review

Smn1  -  survival motor neuron 1

Mus musculus

Synonyms: AI849087, Gemin1, SMN, Smn, Survival motor neuron protein
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Disease relevance of Smn1


High impact information on Smn1

  • In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients [6].
  • The SMA disease gene, termed Survival of Motor Neurons (SMN), is deleted or mutated in over 98% of SMA patients [7].
  • These findings suggest a role for SMN and SIP1 in spliceosomal snRNP biogenesis and function and provide a likely molecular mechanism for the cause of SMA [7].
  • This observation gives strong support to the view that mutations of the SMN gene are responsible for the SMA phenotype as it is the first frameshift mutation reported in SMA [8].
  • The other patients showed either deletions of the SMN gene (49/54) or a gene conversion event changing SMN exon 7 into its highly homologous copy (cBCD541, 1/54) [8].

Chemical compound and disease context of Smn1


Biological context of Smn1

  • Together, these data indicate that ZPR1 contributes to the regulation of SMN complexes and that it is essential for cell survival [11].
  • We have cloned the murine homolog Smn and mapped the gene to Chromosome 13 within the conserved syntenic region of human chromosome 5q13 [12].
  • The predicted amino acid sequence between mouse and human SMN is 82% identical, and a putative nuclear localization signal is conserved [12].
  • Overall, our results indicate that Smn is single copy within the mouse genome, which should facilitate gene disruption experiments to create an animal model of SMA [12].
  • Photobleaching and fluorescence resonance energy transfer experiments demonstrate that coilin and SMN can interact within CBs, but their interaction is not the major determinant of their residence times [13].

Anatomical context of Smn1

  • Neuronal degeneration in spinal muscular atrophy is caused by reduced expression of the survival motor neuron (SMN) protein [14].
  • Sip1 is highly expressed in the spinal cord during early development and expression decreases in parallel with Smn during postnatal development [15].
  • The finding that expression of Sip1 and Smn is tightly co-regulated, together with the unique localization of Smn in neurites, may help in understanding the motor neuron-specific defects observed in SMA patients [15].
  • Strikingly, reduced production of Smn as observed in cell lines derived from SMA patients or in a mouse model for SMA coincides with a simultaneous reduction of Sip1 [15].
  • Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle [16].

Associations of Smn1 with chemical compounds

  • Finally, three biallelic markers were identified within the Smn coding region; two are silent polymorphisms, whereas the third changes a cysteine residue to a tyrosine residue in exon 7 [12].
  • We tested whether profilins interact with SMN via its polyproline stretches [9].
  • Activation of the cAMP pathway by dibutyryl cAMP (0.5 mm) alone or in combination with forskolin (20 microm) caused a 2-5-fold increase in the SMN promoter activity but had no effect on the CRE-II mutated promoter [17].
  • Intraperitoneal injection of epinephrine in mice expressing two copies of the human SMN2 gene resulted in a 2-fold increase in full-length SMN transcript in the liver [17].
  • The SMN gene encodes a 38-kDa protein that localises in the cytoplasm and in nuclear bodies termed Gemini of coiled bodies (gems) [18].

Physical interactions of Smn1

  • Our data demonstrate that full-length coilin is essential for proper formation and/or maintenance of CBs and that recruitment of snRNP and SMN complex proteins to these nuclear subdomains requires sequences within the coilin COOH terminus [1].
  • SMN and the tightly interacting Gemin2 form part of a macromolecular complex (SMN complex) that mediates assembly of spliceosomal small nuclear ribonucleoproteins (U snRNPs) [14].
  • SMN also binds to the small actin-binding protein, profilin [19].

Regulatory relationships of Smn1

  • Using model cell systems and pulse-labeling experiments, we further show that SMN activity and snRNP synthesis are strongly downregulated upon neuronal as well as myogenic differentiation, and linked to the rate of global transcription of postmitotic neurons and myotubes [4].
  • Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates [19].

Other interactions of Smn1

  • Reduced Smn/Gemin2 protein levels lead to disturbed U snRNP assembly as indicated by reduced nuclear accumulation of Sm proteins [14].
  • Using these methods, we detected at least four copies of Naip exon 5 clustering distal to Smn [12].
  • While no new Lgn1 candidates emerged, we have identified new genetic markers that exclude Smn as an Lgn1 candidate [20].
  • Coilin and SMN complex members exhibit relatively long CB residence times, whereas components of snRNPs, small nucleolar RNPs, and factors shared with the nucleolus have significantly shorter residence times [13].
  • One potential modifier gene is represented by ZPR1, which is down-regulated in patients with SMA and encodes a zinc finger protein that interacts with complexes formed by SMN [21].

Analytical, diagnostic and therapeutic context of Smn1


  1. Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product. Tucker, K.E., Berciano, M.T., Jacobs, E.Y., LePage, D.F., Shpargel, K.B., Rossire, J.J., Chan, E.K., Lafarga, M., Conlon, R.A., Matera, A.G. J. Cell Biol. (2001) [Pubmed]
  2. A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy. Monani, U.R., Pastore, M.T., Gavrilina, T.O., Jablonka, S., Le, T.T., Andreassi, C., DiCocco, J.M., Lorson, C., Androphy, E.J., Sendtner, M., Podell, M., Burghes, A.H. J. Cell Biol. (2003) [Pubmed]
  3. Deletion of murine SMN exon 7 directed to skeletal muscle leads to severe muscular dystrophy. Cifuentes-Diaz, C., Frugier, T., Tiziano, F.D., Lacène, E., Roblot, N., Joshi, V., Moreau, M.H., Melki, J. J. Cell Biol. (2001) [Pubmed]
  4. The activity of the spinal muscular atrophy protein is regulated during development and cellular differentiation. Gabanella, F., Carissimi, C., Usiello, A., Pellizzoni, L. Hum. Mol. Genet. (2005) [Pubmed]
  5. Survival motor neuron (SMN) protein: role in neurite outgrowth and neuromuscular maturation during neuronal differentiation and development. Fan, L., Simard, L.R. Hum. Mol. Genet. (2002) [Pubmed]
  6. A mouse model for spinal muscular atrophy. Hsieh-Li, H.M., Chang, J.G., Jong, Y.J., Wu, M.H., Wang, N.M., Tsai, C.H., Li, H. Nat. Genet. (2000) [Pubmed]
  7. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Liu, Q., Fischer, U., Wang, F., Dreyfuss, G. Cell (1997) [Pubmed]
  8. A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients. Bussaglia, E., Clermont, O., Tizzano, E., Lefebvre, S., Bürglen, L., Cruaud, C., Urtizberea, J.A., Colomer, J., Munnich, A., Baiget, M. Nat. Genet. (1995) [Pubmed]
  9. A role for polyproline motifs in the spinal muscular atrophy protein SMN. Profilins bind to and colocalize with smn in nuclear gems. Giesemann, T., Rathke-Hartlieb, S., Rothkegel, M., Bartsch, J.W., Buchmeier, S., Jockusch, B.M., Jockusch, H. J. Biol. Chem. (1999) [Pubmed]
  10. The SMN genes are subject to transcriptional regulation during cellular differentiation. Germain-Desprez, D., Brun, T., Rochette, C., Semionov, A., Rouget, R., Simard, L.R. Gene (2001) [Pubmed]
  11. ZPR1 is essential for survival and is required for localization of the survival motor neurons (SMN) protein to Cajal bodies. Gangwani, L., Flavell, R.A., Davis, R.J. Mol. Cell. Biol. (2005) [Pubmed]
  12. Cloning, characterization, and copy number of the murine survival motor neuron gene: homolog of the spinal muscular atrophy-determining gene. DiDonato, C.J., Chen, X.N., Noya, D., Korenberg, J.R., Nadeau, J.H., Simard, L.R. Genome Res. (1997) [Pubmed]
  13. In vivo kinetics of Cajal body components. Dundr, M., Hebert, M.D., Karpova, T.S., Stanek, D., Xu, H., Shpargel, K.B., Meier, U.T., Neugebauer, K.M., Matera, A.G., Misteli, T. J. Cell Biol. (2004) [Pubmed]
  14. Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death. Jablonka, S., Holtmann, B., Meister, G., Bandilla, M., Rossoll, W., Fischer, U., Sendtner, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  15. Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Jablonka, S., Bandilla, M., Wiese, S., Bühler, D., Wirth, B., Sendtner, M., Fischer, U. Hum. Mol. Genet. (2001) [Pubmed]
  16. Intact satellite cells lead to remarkable protection against Smn gene defect in differentiated skeletal muscle. Nicole, S., Desforges, B., Millet, G., Lesbordes, J., Cifuentes-Diaz, C., Vertes, D., Cao, M.L., De Backer, F., Languille, L., Roblot, N., Joshi, V., Gillis, J.M., Melki, J. J. Cell Biol. (2003) [Pubmed]
  17. Identification of a novel cyclic AMP-response element (CRE-II) and the role of CREB-1 in the cAMP-induced expression of the survival motor neuron (SMN) gene. Majumder, S., Varadharaj, S., Ghoshal, K., Monani, U., Burghes, A.H., Jacob, S.T. J. Biol. Chem. (2004) [Pubmed]
  18. Ultrastructural characterisation of a nuclear domain highly enriched in survival of motor neuron (SMN) protein. Malatesta, M., Scassellati, C., Meister, G., Plöttner, O., Bühler, D., Sowa, G., Martin, T.E., Keidel, E., Fischer, U., Fakan, S. Exp. Cell Res. (2004) [Pubmed]
  19. A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells. Sharma, A., Lambrechts, A., Hao, l.e. .T., Le, T.T., Sewry, C.A., Ampe, C., Burghes, A.H., Morris, G.E. Exp. Cell Res. (2005) [Pubmed]
  20. Comparative sequence analysis of the mouse and human Lgn1/SMA interval. Endrizzi, M., Huang, S., Scharf, J.M., Kelter, A.R., Wirth, B., Kunkel, L.M., Miller, W., Dietrich, W.F. Genomics (1999) [Pubmed]
  21. Deficiency of the zinc finger protein ZPR1 causes neurodegeneration. Doran, B., Gherbesi, N., Hendricks, G., Flavell, R.A., Davis, R.J., Gangwani, L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy. Lesbordes, J.C., Cifuentes-Diaz, C., Miroglio, A., Joshi, V., Bordet, T., Kahn, A., Melki, J. Hum. Mol. Genet. (2003) [Pubmed]
  23. Expression of the SMN gene, the spinal muscular atrophy determining gene, in the mammalian central nervous system. Battaglia, G., Princivalle, A., Forti, F., Lizier, C., Zeviani, M. Hum. Mol. Genet. (1997) [Pubmed]
  24. Development of a gene therapy strategy for the restoration of survival motor neuron protein expression: implications for spinal muscular atrophy therapy. DiDonato, C.J., Parks, R.J., Kothary, R. Hum. Gene Ther. (2003) [Pubmed]
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