A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy

Molecular and Cellular Biology

Volumn 32, Issue 1, 2012, Pages 126-138

  Ruggiu, Matteo ^a,b   McGovern, Vicki L ^c   Lotti, Francesco ^a,b   Saieva, Luciano ^a,b   Li, Darrick K ^a,b   Kariya, Shingo ^a,b   Monani, Umrao R ^a,b   Burghes, Arthur H M ^c   Pellizzoni, Livio ^a,b  

^a NewYork Presbyterian Hospital   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

^c OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; SURVIVAL MOTOR NEURON PROTEIN 1; SURVIVAL MOTOR NEURON PROTEIN 2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DISEASE EXACERBATION; DNA SPLICING; EXON; EXON 7; HUMAN; HUMAN CELL; IN VIVO STUDY; MAMMAL CELL; MOLECULAR MECHANICS; MOTONEURON; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPINAL MUSCULAR ATROPHY;

ANIMALS; EXONS; MICE; MOTOR NEURONS; MUSCULAR ATROPHY, SPINAL; NIH 3T3 CELLS; RNA SPLICING; RNA, MESSENGER; SMN COMPLEX PROTEINS; SURVIVAL OF MOTOR NEURON 1 PROTEIN; SURVIVAL OF MOTOR NEURON 2 PROTEIN;

EID: 84863011418     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.06077-11     Document Type: Article

References (64)

1. Arber S, et al. 1999. Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity. Neuron 23:659-674.
2. Baccon J, Pellizzoni L, Rappsilber J, Mann M, Dreyfuss G. 2002. Identification and characterization of Gemin7, a novel component of the survival of motor neuron complex. J. Biol. Chem. 277:31957-31962.
3. Battle DJ, et al. 2006. The SMN complex: an assembly machine for RNPs. Cold Spring Harbor Symp. Quant. Biol. 71:313-320.
4. Baumer D, et al. 2009. Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genet. 5:e1000773.
5. Bebee TW, Gladman JT, Chandler DS. 2010. Splicing regulation of the survival motor neuron genes and implications for treatment of spinal muscular atrophy. Front. Biosci. 15:1191-1204.
6. Bernal S, et al. 2010. 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. 47:640-642.
7. Briata P, et al. 2005. p38-dependent phosphorylation of the mRNA decay-promoting factor KSRP controls the stability of select myogenic transcripts. Mol. Cell 20:891-903.
8. Burghes AH, Beattie CE. 2009. Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat. Rev. Neurosci. 10:597-609.
9. Burnett BG, et al. 2009. Regulation of SMN protein stability. Mol. Cell. Biol. 29:1107-1115.
10. Carissimi C, et al. 2005. Unrip is a component of SMN complexes active in snRNP assembly. FEBS Lett. 579:2348-2354.
11. Carissimi C, et al. 2006. Gemin8 is a novel component of the survival motor neuron complex and functions in small nuclear ribonucleoprotein assembly. J. Biol. Chem. 281:8126-8134.
12. Cartegni L, Hastings ML, Calarco JA, de Stanchina E, Krainer AR. 2006. Determinants of exon 7 splicing in the spinal muscular atrophy genes, SMN1 and SMN2. Am. J. Hum. Genet. 78:63-77.
13. Cartegni L, Krainer AR. 2002. Disruption of an SF2/ASF-dependent exonic splicing enhancer in SMN2 causes spinal muscular atrophy in the absence of SMN1. Nat. Genet. 30:377-384.
14. Chari A, et al. 2008. An assembly chaperone collaborates with the SMN complex to generate spliceosomal snRNPs. Cell 135:497-509.
15. Chari A, Paknia E, Fischer U. 2009. The role of RNP biogenesis in spinal muscular atrophy. Curr. Opin. Cell Biol. 21:387-393.
16. Charroux B, et al. 1999. 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. 147:1181-1194.
17. Charroux B, et al. 2000. Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli. J. Cell Biol. 148:1177-1186.
18. Cho S, Dreyfuss G. 2010. A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity. Genes Dev. 24: 438-442.
19. Coovert DD, et al. 1997. The survival motor neuron protein in spinal muscular atrophy. Hum. Mol. Genet. 6:1205-1214.
20. Corti S, et al. 2008. Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy. J. Clin. Invest. 118:3316-3330.
21. Fischer U, Liu Q, Dreyfuss G. 1997. The SMN-SIP1 complex has an essential role in spliceosomal snRNP biogenesis. Cell 90:1023-1029.
22. Gabanella F, et al. 2007. Ribonucleoprotein assembly defects correlate with spinal muscular atrophy severity and preferentially affect a subset of spliceosomal snRNPs. PLoS One 2:e921.
23. Gavrilov DK, Shi X, Das K, Gilliam TC, Wang CH. 1998. Differential SMN2 expression associated with SMA severity. Nat. Genet. 20:230-231.
24. Gherzi R, et al. 2004. A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol. Cell 14:571-583.
25. Gubitz AK, et al. 2002. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. J. Biol. Chem. 277:5631-5636.
26. Helmken C, et al. 2003. Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1. Hum. Genet. 114:11-21.
27. Hubers L, et al. 2011. HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects. Hum. Mol. Genet. 20:553-579.
28. Jablonka S, et al. 2002. Gene targeting of Gemin2 in mice reveals a correlation between defects in the biogenesis of U snRNPs and motoneuron cell death. Proc. Natl. Acad. Sci. U. S. A. 99:10126-10131.
29. Jodelka FM, Ebert AD, Duelli DM, Hastings ML. 2010. A feedback loop regulates splicing of the spinal muscular atrophy-modifying gene, SMN2. Hum. Mol. Genet. 19:4906-4917.
30. Kashima T, Manley JL. 2003. A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy. Nat. Genet. 34:460-463.
31. Kataoka N, Dreyfuss G. 2008. Preparation of efficient splicing extracts from whole cells, nuclei, and cytoplasmic fractions. Methods Mol. Biol. 488:357-365.
32. Le TT, et al. 2005. SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN. Hum. Mol. Genet. 14:845-857.
33. Lefebvre S, et al. 1995. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80:155-165.
34. Lefebvre S, et al. 1997. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat. Genet. 16:265-269.
35. Liu Q, Fischer U, Wang F, Dreyfuss G. 1997. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell 90:1013-1021.
36. Lorson CL, Androphy EJ. 2000. An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN. Hum. Mol. Genet. 9:259-265.
37. Lorson CL, Hahnen E, Androphy EJ, Wirth B. 1999. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proc. Natl. Acad. Sci. U. S. A. 96:6307-6311.
38. Lunn MR, Wang CH. 2008. Spinal muscular atrophy. Lancet 371: 2120-2133.
39. Martins de Araujo M, Bonnal S, Hastings ML, Krainer AR, Valcarcel J. 2009. Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP. RNA 15:515-523.
40. Matera AG, Terns RM, Terns MP. 2007. Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8:209-220.
41. McAndrew PE, et al. 1997. Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number. Am. J. Hum. Genet. 60:1411-1422.
42. McGovern VL, Gavrilina TO, Beattie CE, Burghes AH. 2008. Embryonic motor axon development in the severe SMA mouse. Hum. Mol. Genet. 17:2900-2909.
43. Meister G, Buhler D, Pillai R, Lottspeich F, Fischer U. 2001. A multiprotein complex mediates the ATP-dependent assembly of spliceosomal U snRNPs. Nat. Cell Biol. 3:945-949.
44. Monani UR. 2005. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron 48:885-896.
45. Monani UR, et al. 1999. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum. Mol. Genet. 8:1177-1183.
46. Monani UR, et al. 2000. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum. Mol. Genet. 9:333-339.
47. Neuenkirchen N, Chari A, Fischer U. 2008. Deciphering the assembly pathway of Sm-class U snRNPs. FEBS Lett. 582:1997-2003.
48. Olaso R, et al. 2006. Activation of RNA metabolism-related genes in mouse but not human tissues deficient in SMN. Physiol. Genomics 24: 97-104.
49. Passini MA, Cheng SH. 2011. Prospects for the gene therapy of spinal muscular atrophy. Trends Mol. Med. 17:259-265.
50. Pearn J. 1978. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J. Med. Genet. 15:409-413.
51. Pedrotti S, et al. 2010. The splicing regulator Sam68 binds to a novel exonic splicing silencer and functions in SMN2 alternative splicing in spinal muscular atrophy. EMBO J. 29:1235-1247.
52. Pellizzoni L. 2007. Chaperoning ribonucleoprotein biogenesis in health and disease. EMBO Rep. 8:340-345.
53. Pellizzoni L, Baccon J, Rappsilber J, Mann M, Dreyfuss G. 2002. Purification of native survival of motor neurons complexes and identification of Gemin6 as a novel component. J. Biol. Chem. 277:7540-7545.
54. Pellizzoni L, Yong J, Dreyfuss G. 2002. Essential role for the SMN complex in the specificity of snRNP assembly. Science 298:1775-1779.
55. Prior TW, et al. 2009. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am. J. Hum. Genet. 85:408-413.
56. Russman BS. 2007. Spinal muscular atrophy: clinical classification and disease heterogeneity. J. Child Neurol. 22:946-951.
57. Singh NN, Androphy EJ, Singh RN. 2004. In vivo selection reveals combinatorial controls that define a critical exon in the spinal muscular atrophy genes. RNA 10:1291-1305.
58. Singh NN, Singh RN, Androphy EJ. 2007. Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucleic Acids Res. 35:371-389.
59. Tadesse H, Deschenes-Furry J, Boisvenue S, Cote J. 2008. KH-type splicing regulatory protein interacts with survival motor neuron protein and is misregulated in spinal muscular atrophy. Hum. Mol. Genet. 17: 506-524.
60. Vezain M, et al. 2010. 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. 31: E1110-1125.
61. Will CL, Luhrmann R. 2001. Spliceosomal UsnRNP biogenesis, structure and function. Curr. Opin. Cell Biol. 13:290-301.
62. Winkler C, et al. 2005. Reduced U snRNP assembly causes motor axon degeneration in an animal model for spinal muscular atrophy. Genes Dev. 19:2320-2330.
63. Workman E, et al. 2009. A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice. Hum. Mol. Genet. 18: 2215-2229.
64. Zhang Z, et al. 2008. SMN deficiency causes tissue-specific perturbations in the repertoire of snRNAs and widespread defects in splicing. Cell 133: 585-600.