SMN2

Summary

Gene Symbol: SMN2
Description: survival of motor neuron 2, centromeric
Alias: BCD541, C-BCD541, GEMIN1, SMNC, TDRD16B, survival motor neuron protein, component of gems 1, gemin-1, tudor domain containing 16B
Species: human
Products:     SMN2

Top Publications

  1. Singh N, Singh N, Androphy E, Singh R. Splicing of a critical exon of human Survival Motor Neuron is regulated by a unique silencer element located in the last intron. Mol Cell Biol. 2006;26:1333-46 pubmed
    Humans have two nearly identical copies of the Survival Motor Neuron (SMN) gene, SMN1 and SMN2. In spinal muscular atrophy (SMA), SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7...
  2. Cartegni L, Krainer A. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat Genet. 2002;30:377-84 pubmed
    ..survival of motor neuron 1 gene (SMN1), even though all affected individuals carry a nearly identical, normal SMN2 gene...
  3. Paushkin S, Gubitz A, Massenet S, Dreyfuss G. The SMN complex, an assemblyosome of ribonucleoproteins. Curr Opin Cell Biol. 2002;14:305-12 pubmed
  4. Kashima T, Manley J. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat Genet. 2003;34:460-3 pubmed
    ..Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2)...
  5. Pedrotti S, Bielli P, Paronetto M, Ciccosanti F, Fimia G, Stamm S, et al. The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy. EMBO J. 2010;29:1235-47 pubmed publisher
    ..An almost identical SMN2 gene is unable to compensate for this deficiency because a single C-to-T transition at position +6 in exon-7 causes ..
  6. Boda B, Mas C, Giudicelli C, Nepote V, Guimiot F, Levacher B, et al. Survival motor neuron SMN1 and SMN2 gene promoters: identical sequences and differential expression in neurons and non-neuronal cells. Eur J Hum Genet. 2004;12:729-37 pubmed
    ..of motor neuron 1 gene (SMN1) is the main cause of SMA, but disease severity depends primarily on the number of SMN2 gene copies...
  7. Singh N, Androphy E, Singh R. An extended inhibitory context causes skipping of exon 7 of SMN2 in spinal muscular atrophy. Biochem Biophys Res Commun. 2004;315:381-8 pubmed
    SMN1 and SMN2 represent the two nearly identical copies of the survival of motor neuron gene in humans...
  8. Pellizzoni L, Kataoka N, Charroux B, Dreyfuss G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell. 1998;95:615-24 pubmed
    ..These findings demonstrate that SMN plays a crucial role in the generation of the pre-mRNA splicing machinery and thus in mRNA biogenesis, and they link the function of SMN in this pathway to SMA. ..
  9. Kashima T, Rao N, David C, Manley J. hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. Hum Mol Genet. 2007;16:3149-59 pubmed
    ..SMN1 has been duplicated in humans to create SMN2, which produces a low level of functional SMN protein...

More Information

Publications76

  1. Echaniz Laguna A, Guiraud Chaumeil C, Tranchant C, Reeber A, Melki J, Warter J. Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): a potential susceptibility factor for adult-onset lower motor neuron disease. J Neurol. 2002;249:290-3 pubmed
    ..In contrast, the role of the centromeric copy of the SMN gene (SMN2) in MND remains unclear...
  2. Veldink J, Kalmijn S, Van der Hout A, Lemmink H, Groeneveld G, Lummen C, et al. SMN genotypes producing less SMN protein increase susceptibility to and severity of sporadic ALS. Neurology. 2005;65:820-5 pubmed
    ..variants: SMN1, the causative gene responsible for the production of the majority of functional SMN protein, and SMN2, responsible for the production of less protein but sufficient for modifying the SMA phenotype...
  3. Mourelatos Z, Abel L, Yong J, Kataoka N, Dreyfuss G. SMN interacts with a novel family of hnRNP and spliceosomal proteins. EMBO J. 2001;20:5443-52 pubmed
    ..We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a molecular link between the SMN complex and splicing. ..
  4. Wolstencroft E, Mattis V, Bajer A, Young P, Lorson C. A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels. Hum Mol Genet. 2005;14:1199-210 pubmed
    ..In virtually all SMA patients, a nearly identical copy gene is present, SMN2. SMN2 cannot fully compensate for the loss of SMN1 because the majority of transcripts derived from SMN2 lack a ..
  5. Chari A, Golas M, Klingenhäger M, Neuenkirchen N, Sander B, Englbrecht C, et al. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell. 2008;135:497-509 pubmed publisher
    ..The mode of action of this combined chaperone/catalyst system is reminiscent of the mechanism employed by DNA clamp loaders. ..
  6. Wang C, Jong Y, Chang J, Chen Y, Wu S. Universal fluorescent multiplex PCR and capillary electrophoresis for evaluation of gene conversion between SMN1 and SMN2 in spinal muscular atrophy. Anal Bioanal Chem. 2010;397:2375-83 pubmed publisher
    ..electrophoresis (CE) method with universal fluorescent multiplex PCR to simultaneously detect the SMN1 and SMN2 genes in exons 7 and 8...
  7. Singh N, Seo J, Ottesen E, Shishimorova M, Bhattacharya D, Singh R. TIA1 prevents skipping of a critical exon associated with spinal muscular atrophy. Mol Cell Biol. 2011;31:935-54 pubmed publisher
    Prevention of skipping of exon 7 during pre-mRNA splicing of Survival Motor Neuron 2 (SMN2) holds the promise for cure of spinal muscular atrophy (SMA), a leading genetic cause of infant mortality...
  8. Chen T, Tzeng C, Wang C, Wu S, Chang J, Yang S, et al. Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population. J Neurol Sci. 2011;308:83-7 pubmed publisher
    ..The survival motor neuron 1 (SMN1) gene is an SMA-determining gene and SMN2 represents an SMA-modifying gene...
  9. Bebee T, Gladman J, Chandler D. Splicing of the Survival Motor Neuron genes and implications for treatment of SMA. Front Biosci (Landmark Ed). 2010;15:1191-1204 pubmed
    ..The reduced SMN levels are due to loss of the survival motor neuron-1 (SMN1) gene. Humans carry a nearly identical SMN2 gene that generates a truncated protein, due to a C to T nucleotide alteration in exon 7 that leads to inefficient ..
  10. Young P, Man N, Lorson C, Le T, Androphy E, Burghes A, et al. The exon 2b region of the spinal muscular atrophy protein, SMN, is involved in self-association and SIP1 binding. Hum Mol Genet. 2000;9:2869-77 pubmed
    ..The presence of two separate self-association sites suggests a novel mechanism by which linear oligomers or closed rings might be formed from SMN monomers. ..
  11. Sheng Yuan Z, Xiong F, Chen Y, Yan T, Zeng J, Li L, et al. Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population. Eur J Hum Genet. 2010;18:978-84 pubmed publisher
    ..The results presented 13 groups with different SMN1/SMN2 ratios among 1712 newborn individuals, which corresponded to 1535 subjects with two copies of SMN1, 119 with three ..
  12. Kernochan L, Russo M, Woodling N, Huynh T, Avila A, Fischbeck K, et al. The role of histone acetylation in SMN gene expression. Hum Mol Genet. 2005;14:1171-82 pubmed
    Increasing survival motor neuron 2 (SMN2) gene expression may be an effective strategy for the treatment of spinal muscular atrophy (SMA)...
  13. Echaniz Laguna A, Miniou P, Bartholdi D, Melki J. The promoters of the survival motor neuron gene (SMN) and its copy (SMNc) share common regulatory elements. Am J Hum Genet. 1999;64:1365-70 pubmed
    ..SMN is duplicated, and the almost identical copy gene (SMNc) remains functional in patients with SMA...
  14. Meister G, Buhler 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. Hum Mol Genet. 2000;9:1977-86 pubmed
    ..This shows that the SMN-Sm protein interaction is not restricted to the cytoplasm. Our data imply that nuclear SMN affects splicing by modulating the Sm protein composition of U snRNPs. ..
  15. Watihayati M, Fatemeh H, Marini M, Atif A, Zahiruddin W, Sasongko T, et al. Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy. Brain Dev. 2009;31:42-5 pubmed publisher
    ..The SMN2 gene is highly homologous to SMN1 and has been reported to be correlated with severity of the disease...
  16. Brichta L, Hofmann Y, Hahnen E, Siebzehnrubl F, Raschke H, Blumcke I, et al. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet. 2003;12:2481-9 pubmed
    ..motor neuron gene (SMN1) is the primary cause of SMA, while SMA severity is mainly determined by the number of SMN2 copies...
  17. Yuo C, Lin H, Chang Y, Yang W, Chang J. 5-(N-ethyl-N-isopropyl)-amiloride enhances SMN2 exon 7 inclusion and protein expression in spinal muscular atrophy cells. Ann Neurol. 2008;63:26-34 pubmed
    ..All SMA patients carry at least one copy of a nearly identical SMN2 gene...
  18. Selenko P, Sprangers R, Stier G, Buhler D, Fischer U, Sattler M. SMN tudor domain structure and its interaction with the Sm proteins. Nat Struct Biol. 2001;8:27-31 pubmed
    ..Our data provide a structural basis for a molecular defect underlying SMA. ..
  19. Sun Y, Grimmler M, Schwarzer V, Schoenen F, Fischer U, Wirth B. Molecular and functional analysis of intragenic SMN1 mutations in patients with spinal muscular atrophy. Hum Mutat. 2005;25:64-71 pubmed
    ..The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts ..
  20. Zhang R, So B, Li P, Yong J, Glisovic T, Wan L, et al. Structure of a key intermediate of the SMN complex reveals Gemin2's crucial function in snRNP assembly. Cell. 2011;146:384-95 pubmed publisher
    ..These findings provide insight into SMN complex assembly and specificity, linking snRNP biogenesis and SMA pathogenesis. ..
  21. Corcia P, Camu W, Halimi J, Vourc H P, Antar C, Vedrine S, et al. SMN1 gene, but not SMN2, is a risk factor for sporadic ALS. Neurology. 2006;67:1147-50 pubmed
    SMN1 gene deletions cause spinal muscular atrophy, and SMN2 gene deletions have been associated with sporadic lower motor neuron diseases...
  22. Elsheikh B, Prior T, Zhang X, Miller R, Kolb S, Moore D, et al. An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy. Muscle Nerve. 2009;40:652-6 pubmed publisher
    To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies)...
  23. Sumner C, Kolb S, Harmison G, Jeffries N, Schadt K, Finkel R, et al. SMN mRNA and protein levels in peripheral blood: biomarkers for SMA clinical trials. Neurology. 2006;66:1067-73 pubmed
    ..SMN1 and SMN2 gene copy numbers were determined in blood samples collected from 86 subjects...
  24. Rudnik Schoneborn S, Heller R, Berg C, Betzler C, Grimm T, Eggermann T, et al. Congenital heart disease is a feature of severe infantile spinal muscular atrophy. J Med Genet. 2008;45:635-8 pubmed publisher
    ..The presence of at least one SMN2 gene copy is required for normal embryogenesis...
  25. Bose J, Wang I, Hung L, Tarn W, Shen C. TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing. J Biol Chem. 2008;283:28852-9 pubmed publisher
    ..Furthermore, both RNA-recognition motif domains are required for its ability to enhance the SMN2 exon 7 inclusion...
  26. Coovert D, Le T, McAndrew P, Strasswimmer J, Crawford T, Mendell J, et al. The survival motor neuron protein in spinal muscular atrophy. Hum Mol Genet. 1997;6:1205-14 pubmed
    ..We suggest that disruption of SMN(T) in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons. ..
  27. Singh R. Evolving concepts on human SMN pre-mRNA splicing. RNA Biol. 2007;4:7-10 pubmed
    SMN1 and SMN2 represent two nearly identical copies of the survival motor neuron gene in humans...
  28. Rossoll W, Kröning A, Ohndorf U, 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?. Hum Mol Genet. 2002;11:93-105 pubmed
    ..The human genome, in contrast to mouse, contains a second SMN gene (SMN2) which codes for a gene product which is alternatively spliced at the C-terminus, but also gives rise to low levels ..
  29. Martins de Araujo M, Bonnal S, Hastings M, Krainer A, Valcarcel J. Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP. RNA. 2009;15:515-23 pubmed publisher
    ..A paralog of the gene, SMN2, cannot provide adequate levels of functional SMN because exon 7 is skipped in a significant fraction of the mature ..
  30. Maranda B, Fan L, Soucy J, Simard L, Mitchell G. Spinal muscular atrophy: clinical validation of a single-tube multiplex real time PCR assay for determination of SMN1 and SMN2 copy numbers. Clin Biochem. 2012;45:88-91 pubmed publisher
    ..We describe a triplex quantitative real-time PCR method in which fragments of SMN1, SMN2 (a nearly-identical neighboring gene with markedly reduced function) and of a control gene, CFTR, are amplified in ..
  31. Monani U, Lorson C, Parsons D, Prior T, Androphy E, Burghes A, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet. 1999;8:1177-83 pubmed
    ..Alterations within an almost identical copy gene, the centromeric survival motor neuron 2 ( SMN2 ) gene produce no known phenotypic effect...
  32. Burglen L, Lefebvre S, Clermont O, Burlet P, Viollet L, Cruaud C, et al. Structure and organization of the human survival motor neurone (SMN) gene. Genomics. 1996;32:479-82 pubmed
    ..The availability of the human SMN and its highly homologous counterpart (CBCD541) gene structures and exon-intron boundaries will hopefully speed up the characterization of SMN gene mutations in SMA. ..
  33. Bernal S, Alias L, Barceló M, Also Rallo E, Martínez Hernández R, Gamez J, et al. The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor. J Med Genet. 2010;47:640-2 pubmed publisher
    ..A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c...
  34. Tiziano F, Pinto A, Fiori S, Lomastro R, Messina S, Bruno C, et al. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR. Eur J Hum Genet. 2010;18:52-8 pubmed publisher
    ..All patients have at least one or more (usually 2-4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7...
  35. Hauke J, Riessland M, Lunke S, Eyupoglu I, Blumcke I, El Osta A, et al. Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition. Hum Mol Genet. 2009;18:304-17 pubmed publisher
    ..of the survival motor neuron gene 1 (SMN1), while the disease severity is mainly influenced by the number of SMN2 gene copies...
  36. Young P, DiDonato C, Hu D, Kothary R, Androphy E, Lorson C. SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1. Hum Mol Genet. 2002;11:577-87 pubmed
    Proximal spinal muscular atrophy (SMA) is caused by the homozygous loss of survival motor neuron (SMN1). SMN2, a nearly identical copy gene, is present in all SMA patients; however this gene cannot provide protection from disease due to ..
  37. Parsons D, McAndrew P, Iannaccone S, Mendell J, Burghes A, Prior T. Intragenic telSMN mutations: frequency, distribution, evidence of a founder effect, and modification of the spinal muscular atrophy phenotype by cenSMN copy number. Am J Hum Genet. 1998;63:1712-23 pubmed
    ..We note that telSMN missense mutations are associated with milder disease in our patients and that the severe type I SMA phenotype caused by frameshift mutations can be ameliorated by an increase in cenSMN gene copy number. ..
  38. Crawford T, Paushkin S, Kobayashi D, Forrest S, JOYCE C, Finkel R, et al. Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS ONE. 2012;7:e33572 pubmed publisher
    The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development...
  39. Bebee T, Dominguez C, Samadzadeh Tarighat S, Akehurst K, Chandler D. Hypoxia is a modifier of SMN2 splicing and disease severity in a severe SMA mouse model. Hum Mol Genet. 2012;21:4301-13 pubmed publisher
    ..Reduced levels of SMN is due to the loss of the SMN1 gene and inefficient splicing of the SMN2 gene caused by a C>T mutation in exon 7...
  40. Kariya S, Park G, Maeno Hikichi Y, Leykekhman O, Lutz C, Arkovitz M, et al. Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet. 2008;17:2552-69 pubmed publisher
    ..Studies involving SMA patients and animal models expressing the human SMN2 gene have yielded relatively little information about the earliest cellular consequences of reduced SMN protein...
  41. Farooq F, Balabanian S, Liu X, Holcik M, MacKenzie A. p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR. Hum Mol Genet. 2009;18:4035-45 pubmed publisher
    ..A potential treatment strategy for SMA is to upregulate levels of SMN protein originating from the SMN2 gene compensating in part for the absence of functional SMN1 gene...
  42. Kim J, Lee S, Choi Y, Kang S, Lee J, Choi J, et al. Association between survivor motor neuron 2 (SMN2) gene homozygous deletion and sporadic lower motor neuron disease in a Korean population. Ann Clin Lab Sci. 2010;40:368-74 pubmed
    ..We genotyped the copy number of SMN1 and SMN2 in 18 patients diagnosed with sporadic LMND and 100 neurologically healthy subjects using the multiplex ligation-..
  43. Feldkötter M, Schwarzer V, Wirth R, Wienker T, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J Hum Genet. 2002;70:358-68 pubmed
    ..b>SMN2, a copy gene, influences the severity of SMA and may be used in somatic gene therapy of patients with SMA in the ..
  44. Hua Y, Sahashi K, Rigo F, Hung G, Horev G, Bennett C, et al. Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model. Nature. 2011;478:123-6 pubmed publisher
    ..Humans have a paralogue, SMN2, whose exon 7 is predominantly skipped, but the limited amount of functional, full-length SMN protein expressed ..
  45. Buhler D, Raker V, Luhrmann R, Fischer U. Essential role for the tudor domain of SMN in spliceosomal U snRNP assembly: implications for spinal muscular atrophy. Hum Mol Genet. 1999;8:2351-7 pubmed
    ..Thus, our data show that SMN is an essential U snRNP assembly factor and establish a direct correlation between defects in the biogenesis of U snRNPs and SMA. ..
  46. Hebert M, Szymczyk P, Shpargel K, Matera A. Coilin forms the bridge between Cajal bodies and SMN, the spinal muscular atrophy protein. Genes Dev. 2001;15:2720-9 pubmed
    ..A cardinal feature of SMA patient cells is a defect in the targeting of SMN to nuclear foci; our results uncover a role for coilin in this process...
  47. Cho S, Moon H, Loh T, Oh H, Cho S, Choy H, et al. hnRNP M facilitates exon 7 inclusion of SMN2 pre-mRNA in spinal muscular atrophy by targeting an enhancer on exon 7. Biochim Biophys Acta. 2014;1839:306-15 pubmed publisher
    ..Although SMA patients include SMN2 gene, a duplicate of SMN1 gene, predominant production of exon 7 skipped isoform from SMN2 pre-mRNA, fails to ..
  48. Jodelka F, Ebert A, Duelli D, Hastings M. A feedback loop regulates splicing of the spinal muscular atrophy-modifying gene, SMN2. Hum Mol Genet. 2010;19:4906-17 pubmed publisher
    ..SMN protein is also encoded by SMN2. However, splicing of SMN2 exon 7 is defective, and consequently, the majority of the transcripts produce a ..
  49. Doktor T, Schroeder L, Vested A, Palmfeldt J, Andersen H, Gregersen N, et al. SMN2 exon 7 splicing is inhibited by binding of hnRNP A1 to a common ESS motif that spans the 3' splice site. Hum Mutat. 2011;32:220-30 pubmed publisher
    Spinal Muscular Atrophy is caused by homozygous loss of SMN1 with phenotypic modulation by SMN2. SMN2 expresses only limited amounts of full-length transcript due to skipping of exon 7 caused by disruption of an SF2/ASF binding ESE...
  50. Talbot K, Ponting C, Theodosiou A, Rodrigues N, Surtees R, Mountford R, et al. Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?. Hum Mol Genet. 1997;6:497-500 pubmed
    ..We have identified apparent orthologues of SMN in Caenorhabditis elegans and Schizosaccharomyces pombe. These sequences retain the highly conserved Y-G motif and provide additional support for a role of SMN in mRNA metabolism. ..
  51. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155-65 pubmed
    ..These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene. ..
  52. Charroux B, Pellizzoni L, Perkinson R, 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. J Cell Biol. 1999;147:1181-94 pubmed
    ..The presence of a DEAD box motif in Gemin3 suggests that it may provide the catalytic activity that plays a critical role in the function of the SMN complex on RNPs. ..
  53. Kashima T, Rao N, Manley J. An intronic element contributes to splicing repression in spinal muscular atrophy. Proc Natl Acad Sci U S A. 2007;104:3426-31 pubmed
    ..b>SMN2 is a nearly identical copy of SMN1 that is unable to prevent disease, because most SMN2 transcripts lack exon 7 and ..
  54. Gennarelli M, Lucarelli M, Capon F, Pizzuti A, Merlini L, Angelini C, et al. Survival motor neuron gene transcript analysis in muscles from spinal muscular atrophy patients. Biochem Biophys Res Commun. 1995;213:342-8 pubmed
    ..Our results suggest that multiple RNA splicing is operative in the two SMN-related genes and that SMN-related polypeptides may be active in the muscle. ..
  55. Narayanan U, Achsel T, Luhrmann R, Matera A. Coupled in vitro import of U snRNPs and SMN, the spinal muscular atrophy protein. Mol Cell. 2004;16:223-34 pubmed
    ..Thus, import of SMN and U snRNPs are coupled in vitro. Furthermore, we identify nuclear import defects in SMA patient-derived SMN mutants, uncovering a potential mechanism for SMN dysfunction. ..
  56. Gangwani L, Mikrut M, Theroux S, Sharma M, Davis R. Spinal muscular atrophy disrupts the interaction of ZPR1 with the SMN protein. Nat Cell Biol. 2001;3:376-83 pubmed
    ..Similarly, decreased ZPR1 expression prevents SMN localization to nuclear bodies. Our data show that ZPR1 is required for the localization of SMN in nuclear bodies. ..
  57. 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. J Biol Chem. 2002;277:7540-5 pubmed
    ..Co-immunoprecipitation, immunolocalization, and in vitro binding experiments demonstrate that Gemin6 is a component of the SMN complex that localizes to gems and interacts with several Sm proteins of the spliceosomal snRNPs. ..
  58. Friesen W, Dreyfuss G. Specific sequences of the Sm and Sm-like (Lsm) proteins mediate their interaction with the spinal muscular atrophy disease gene product (SMN). J Biol Chem. 2000;275:26370-5 pubmed
    ..These findings demonstrate that arginine- and glycine-rich domains are necessary and sufficient for SMN interaction, and they expand further the range of targets of the SMN protein. ..
  59. 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. J Biol Chem. 2002;277:31957-62 pubmed
    ..With the identification of Gemin7, the inventory of the core components of the SMN complex appears essentially complete. ..
  60. Park G, Maeno Hikichi Y, Awano T, Landmesser L, Monani U. Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene. J Neurosci. 2010;30:12005-19 pubmed publisher
    ..This realization is tempered by the relatively mild SMA phenotype in our model mice, one explanation for which is the presence of normal SMN levels in non-neuronal tissue that serves to modulate disease severity. ..
  61. Irimura S, Kitamura K, Kato N, Saiki K, Takeuchi A, Gunadi -, et al. HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1. Kobe J Med Sci. 2009;54:E227-36 pubmed
    Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical gene, SMN2, fails to compensate for the loss of SMN1 because SMN2 produces mainly an exon 7-skipped product...
  62. Prior T, Krainer A, Hua Y, Swoboda K, Snyder P, Bridgeman S, et al. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet. 2009;85:408-13 pubmed publisher
    ..A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner...
  63. Mailman M, Heinz J, Papp A, Snyder P, Sedra M, Wirth B, et al. Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2. Genet Med. 2002;4:20-6 pubmed publisher
    This study describes SMN1 deletion frequency, carrier studies, and the effect of the modifying SMN2 gene on the spinal muscular atrophy (SMA) phenotype...
  64. Gubitz A, 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. J Biol Chem. 2002;277:5631-6 pubmed
    ..The presence of 13 WD repeat domains in the amino-terminal half of Gemin5 and a coiled-coil motif near its carboxyl terminus indicate that it may form a large heteromeric complex and engage in multiple interactions. ..
  65. Workman E, Saieva L, Carrel T, Crawford T, Liu D, Lutz C, et al. A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Hum Mol Genet. 2009;18:2215-29 pubmed publisher
    ..Loss of the survival motor neuron (SMN1) gene, in the presence of the SMN2 gene causes SMA...
  66. 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. 1997;90:1013-21 pubmed
    ..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. ..
  67. Vezain M, Saugier Veber P, Goina E, Touraine R, Manel V, Toutain A, et al. A rare SMN2 variant in a previously unrecognized composite splicing regulatory element induces exon 7 inclusion and reduces the clinical severity of spinal muscular atrophy. Hum Mutat. 2010;31:E1110-25 pubmed publisher
    ..The disease severity is mainly influenced by the copy number of SMN2, a nearly identical gene from which only low amounts of full-length mRNA are produced...