The SMN2 gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric (SMN1) and centromeric (SMN2) copies of this gene are nearly identical and encode the same protein. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. The nucleotide substitution in SMN2 results in around 80-90% of its transcripts to be a truncated, unstable protein of no biological function (Δ7SMN) and only 10-20% of its transcripts being full-length protein (fl-SMN).[citation needed]
Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3–8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene.[6]
Clinical significance
While mutations in the telomeric copy are associated with spinal muscular atrophy, mutations in this gene, the centromeric copy, do not lead to disease. This gene may be a modifier of disease caused by mutation in the telomeric copy.[citation needed]
^ abcGRCm38: Ensembl release 89: ENSMUSG00000021645 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M (January 1995). "Identification and characterization of a spinal muscular atrophy-determining gene". Cell. 80 (1): 155–65. doi:10.1016/0092-8674(95)90460-3. PMID 7813012. S2CID 14291056.
^ ab"Entrez Gene: SMN2 survival of motor neuron 2, centromeric".
Further reading
Watihayati MS, Fatemeh H, Marini M, Atif AB, Zahiruddin WM, Sasongko TH, Tang TH, Zabidi-Hussin ZA, Nishio H, Zilfalil BA (January 2009). "Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy". Brain & Development. 31 (1): 42–5. doi:10.1016/j.braindev.2008.08.012. PMID 18842367. S2CID 206312220.
Prior TW, Krainer AR, Hua Y, Swoboda KJ, Snyder PC, Bridgeman SJ, Burghes AH, Kissel JT (September 2009). "A positive modifier of spinal muscular atrophy in the SMN2 gene". American Journal of Human Genetics. 85 (3): 408–13. doi:10.1016/j.ajhg.2009.08.002. PMC2771537. PMID 19716110.
Coady TH, Baughan TD, Shababi M, Passini MA, Lorson CL (2008). Valcarcel J (ed.). "Development of a single vector system that enhances trans-splicing of SMN2 transcripts". PLOS ONE. 3 (10): e3468. Bibcode:2008PLoSO...3.3468C. doi:10.1371/journal.pone.0003468. PMC2565107. PMID 18941511.
Elsheikh B, Prior T, Zhang X, Miller R, Kolb SJ, Moore D, Bradley W, Barohn R, Bryan W, Gelinas D, Iannaccone S, Leshner R, Mendell JR, Mendoza M, Russman B, Smith S, King W, Kissel JT (October 2009). "An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy". Muscle & Nerve. 40 (4): 652–6. doi:10.1002/mus.21350. PMID 19760790. S2CID 44901599.
Workman E, Saieva L, Carrel TL, Crawford TO, Liu D, Lutz C, Beattie CE, Pellizzoni L, Burghes AH (June 2009). "A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice". Human Molecular Genetics. 18 (12): 2215–29. doi:10.1093/hmg/ddp157. PMC2685758. PMID 19329542.
Bose JK, Wang IF, Hung L, Tarn WY, Shen CK (October 2008). "TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing". The Journal of Biological Chemistry. 283 (43): 28852–9. doi:10.1074/jbc.M805376200. PMC2661999. PMID 18703504.
Hauke J, Riessland M, Lunke S, Eyüpoglu IY, Blümcke I, El-Osta A, Wirth B, Hahnen E (January 2009). "Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition". Human Molecular Genetics. 18 (2): 304–17. doi:10.1093/hmg/ddn357. PMC2638778. PMID 18971205.
Corcia P, Camu W, Praline J, Gordon PH, Vourch P, Andres C (2009). "The importance of the SMN genes in the genetics of sporadic ALS". Amyotrophic Lateral Sclerosis. 10 (5–6): 436–40. doi:10.3109/17482960902759162. PMID 19922137. S2CID 2326464.
Tiziano FD, Pinto AM, Fiori S, Lomastro R, Messina S, Bruno C, Pini A, Pane M, D'Amico A, Ghezzo A, Bertini E, Mercuri E, Neri G, Brahe C (January 2010). "SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR". European Journal of Human Genetics. 18 (1): 52–8. doi:10.1038/ejhg.2009.116. PMC2987170. PMID 19603064.
Jedrzejowska M, Milewski M, Zimowski J, Borkowska J, Kostera-Pruszczyk A, Sielska D, Jurek M, Hausmanowa-Petrusewicz I (2009). "Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease". Acta Biochimica Polonica. 56 (1): 103–8. doi:10.18388/abp.2009_2521. PMID 19287802.
Arkblad E, Tulinius M, Kroksmark AK, Henricsson M, Darin N (May 2009). "A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy". Acta Paediatrica. 98 (5): 865–72. doi:10.1111/j.1651-2227.2008.01201.x. PMID 19154529. S2CID 3134264.
Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (June 2002). "The SMN complex, an assemblyosome of ribonucleoproteins". Current Opinion in Cell Biology. 14 (3): 305–12. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652.
Farooq F, Balabanian S, Liu X, Holcik M, MacKenzie A (November 2009). "p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR". Human Molecular Genetics. 18 (21): 4035–45. doi:10.1093/hmg/ddp352. PMID 19648294.
Hasanzad M, Golkar Z, Kariminejad R, Hadavi V, Almadani N, Afroozan F, Salahshurifar I, Shafeghati Y, Kahrizi K, Najmabadi H (February 2009). "Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy". Annals of the Academy of Medicine, Singapore. 38 (2): 139–41. PMID 19271042.
Martins de Araújo M, Bonnal S, Hastings ML, Krainer AR, Valcárcel J (April 2009). "Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP". RNA. 15 (4): 515–23. doi:10.1261/rna.1273209. PMC2661831. PMID 19244360.
Song F, Qu YJ, Zou LP, Wang LW, Long MJ, Wang X, Yang YL, Chen Q, Wang H, Jin YW (December 2008). "[Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy]". Zhonghua Er Ke Za Zhi = Chinese Journal of Pediatrics. 46 (12): 919–23. PMID 19134255.
Irimura S, Kitamura K, Kato N, Saiki K, Takeuchi A, Matsuo M, Nishio H, Lee MJ (2009). "HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1". The Kobe Journal of Medical Sciences. 54 (5): E227-36. PMID 19628962.
Yong J, Wan L, Dreyfuss G (May 2004). "Why do cells need an assembly machine for RNA-protein complexes?". Trends in Cell Biology. 14 (5): 226–32. doi:10.1016/j.tcb.2004.03.010. PMID 15130578.
Chen HH, Chang JG, Lu RM, Peng TY, Tarn WY (November 2008). "The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene". Molecular and Cellular Biology. 28 (22): 6929–38. doi:10.1128/MCB.01332-08. PMC2573304. PMID 18794368.
Cogulu O, Durmaz B, Pehlivan S, Alpman A, Ozkinay F (June 2009). "Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy". Genetic Testing and Molecular Biomarkers. 13 (3): 287–8. doi:10.1089/gtmb.2008.0139. PMID 19397406.
smn2, survival, motor, neuron, gene, that, encodes, protein, full, truncated, humans, available, structurespdbortholog, search, pdbe, rcsblist, codes1g5v, 1mhn, 2leh, 3s6n, 4a4e, 4a4g, 4gli, 4nl6, 4nl7, 4qq6identifiersaliases, bcd541, bcd541, gemin1, smnc, tdr. Survival of motor neuron 2 SMN2 is a gene that encodes the SMN protein full and truncated in humans 5 6 SMN2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1G5V 1MHN 2LEH 3S6N 4A4E 4A4G 4GLI 4NL6 4NL7 4QQ6IdentifiersAliasesSMN2 BCD541 C BCD541 GEMIN1 SMNC TDRD16B survival of motor neuron 2 centromeric survival motor neuron 2 centromericExternal IDsOMIM 601627 MGI 109257 HomoloGene 292 GeneCards SMN2Gene location Human Chr Chromosome 5 human 1 Band5q13 2Start70 049 638 bp 1 End70 078 522 bp 1 Gene location Mouse Chr Chromosome 13 mouse 2 Band13 D1 13 52 99 cMStart100 261 360 bp 2 End100 274 198 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inendometriumsmooth muscle tissueright uterine tuberectumbone marrowthymusskeletal muscle tissueanterior pituitaryappendixright coronary arteryTop expressed inyolk sacmorulasecondary oocytesomitemaxillary prominenceneural tubeganglionic eminencemedial ganglionic eminencethymuslipMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein binding RNA binding identical protein bindingCellular componentcytoplasm SMN Sm protein complex cytosol Cajal body nucleoplasm SMN complex Z disc neuron projection cytoplasmic ribonucleoprotein granule nucleus Gemini of coiled bodies perikaryon cell projectionBiological processDNA templated transcription termination mRNA processing nervous system development spliceosomal snRNP assembly spliceosomal complex assembly RNA splicing import into nucleusSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez660720595EnsemblENSG00000277773ENSG00000205571ENSG00000273772ENSMUSG00000021645UniProtQ16637P97801RefSeq mRNA NM 017411NM 022875NM 022876NM 022877NM 001252629NM 011420RefSeq protein NP 059107NP 075013NP 075014NP 075015NP 000335NP 001284644NP 075012NP 001239558NP 035550Location UCSC Chr 5 70 05 70 08 MbChr 13 100 26 100 27 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Gene 2 Clinical significance 3 References 4 Further readingGene EditThe SMN2 gene is part of a 500 kb inverted duplication on chromosome 5q13 This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region The telomeric SMN1 and centromeric SMN2 copies of this gene are nearly identical and encode the same protein The critical sequence difference between the two genes is a single nucleotide in exon 7 which is thought to be an exon splice enhancer The nucleotide substitution in SMN2 results in around 80 90 of its transcripts to be a truncated unstable protein of no biological function D7SMN and only 10 20 of its transcripts being full length protein fl SMN citation needed Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1 2a 2b and 3 8 It is thought that gene conversion events may involve the two genes leading to varying copy numbers of each gene 6 Clinical significance EditWhile mutations in the telomeric copy are associated with spinal muscular atrophy mutations in this gene the centromeric copy do not lead to disease This gene may be a modifier of disease caused by mutation in the telomeric copy citation needed References Edit a b c ENSG00000205571 ENSG00000273772 GRCh38 Ensembl release 89 ENSG00000277773 ENSG00000205571 ENSG00000273772 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000021645 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Lefebvre S Burglen L Reboullet S Clermont O Burlet P Viollet L Benichou B Cruaud C Millasseau P Zeviani M January 1995 Identification and characterization of a spinal muscular atrophy determining gene Cell 80 1 155 65 doi 10 1016 0092 8674 95 90460 3 PMID 7813012 S2CID 14291056 a b Entrez Gene SMN2 survival of motor neuron 2 centromeric Further reading EditWatihayati MS Fatemeh H Marini M Atif AB Zahiruddin WM Sasongko TH Tang TH Zabidi Hussin ZA Nishio H Zilfalil BA January 2009 Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy Brain amp Development 31 1 42 5 doi 10 1016 j braindev 2008 08 012 PMID 18842367 S2CID 206312220 Prior TW Krainer AR Hua Y Swoboda KJ Snyder PC Bridgeman SJ Burghes AH Kissel JT September 2009 A positive modifier of spinal muscular atrophy in the SMN2 gene American Journal of Human Genetics 85 3 408 13 doi 10 1016 j ajhg 2009 08 002 PMC 2771537 PMID 19716110 Coady TH Baughan TD Shababi M Passini MA Lorson CL 2008 Valcarcel J ed Development of a single vector system that enhances trans splicing of SMN2 transcripts PLOS ONE 3 10 e3468 Bibcode 2008PLoSO 3 3468C doi 10 1371 journal pone 0003468 PMC 2565107 PMID 18941511 Elsheikh B Prior T Zhang X Miller R Kolb SJ Moore D Bradley W Barohn R Bryan W Gelinas D Iannaccone S Leshner R Mendell JR Mendoza M Russman B Smith S King W Kissel JT October 2009 An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy Muscle amp Nerve 40 4 652 6 doi 10 1002 mus 21350 PMID 19760790 S2CID 44901599 Workman E Saieva L Carrel TL Crawford TO Liu D Lutz C Beattie CE Pellizzoni L Burghes AH June 2009 A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice Human Molecular Genetics 18 12 2215 29 doi 10 1093 hmg ddp157 PMC 2685758 PMID 19329542 Bose JK Wang IF Hung L Tarn WY Shen CK October 2008 TDP 43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre mRNA splicing The Journal of Biological Chemistry 283 43 28852 9 doi 10 1074 jbc M805376200 PMC 2661999 PMID 18703504 Hauke J Riessland M Lunke S Eyupoglu IY Blumcke I El Osta A Wirth B Hahnen E January 2009 Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition Human Molecular Genetics 18 2 304 17 doi 10 1093 hmg ddn357 PMC 2638778 PMID 18971205 Corcia P Camu W Praline J Gordon PH Vourch P Andres C 2009 The importance of the SMN genes in the genetics of sporadic ALS Amyotrophic Lateral Sclerosis 10 5 6 436 40 doi 10 3109 17482960902759162 PMID 19922137 S2CID 2326464 Tiziano FD Pinto AM Fiori S Lomastro R Messina S Bruno C Pini A Pane M D Amico A Ghezzo A Bertini E Mercuri E Neri G Brahe C January 2010 SMN transcript levels in leukocytes of SMA patients determined by absolute real time PCR European Journal of Human Genetics 18 1 52 8 doi 10 1038 ejhg 2009 116 PMC 2987170 PMID 19603064 Jedrzejowska M Milewski M Zimowski J Borkowska J Kostera Pruszczyk A Sielska D Jurek M Hausmanowa Petrusewicz I 2009 Phenotype modifiers of spinal muscular atrophy the number of SMN2 gene copies deletion in the NAIP gene and probably gender influence the course of the disease Acta Biochimica Polonica 56 1 103 8 doi 10 18388 abp 2009 2521 PMID 19287802 Arkblad E Tulinius M Kroksmark AK Henricsson M Darin N May 2009 A population based study of genotypic and phenotypic variability in children with spinal muscular atrophy Acta Paediatrica 98 5 865 72 doi 10 1111 j 1651 2227 2008 01201 x PMID 19154529 S2CID 3134264 Paushkin S Gubitz AK Massenet S Dreyfuss G June 2002 The SMN complex an assemblyosome of ribonucleoproteins Current Opinion in Cell Biology 14 3 305 12 doi 10 1016 S0955 0674 02 00332 0 PMID 12067652 Farooq F Balabanian S Liu X Holcik M MacKenzie A November 2009 p38 Mitogen activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR Human Molecular Genetics 18 21 4035 45 doi 10 1093 hmg ddp352 PMID 19648294 Hasanzad M Golkar Z Kariminejad R Hadavi V Almadani N Afroozan F Salahshurifar I Shafeghati Y Kahrizi K Najmabadi H February 2009 Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy Annals of the Academy of Medicine Singapore 38 2 139 41 PMID 19271042 Martins de Araujo M Bonnal S Hastings ML Krainer AR Valcarcel J April 2009 Differential 3 splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP RNA 15 4 515 23 doi 10 1261 rna 1273209 PMC 2661831 PMID 19244360 Song F Qu YJ Zou LP Wang LW Long MJ Wang X Yang YL Chen Q Wang H Jin YW December 2008 Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy Zhonghua Er Ke Za Zhi Chinese Journal of Pediatrics 46 12 919 23 PMID 19134255 Irimura S Kitamura K Kato N Saiki K Takeuchi A Matsuo M Nishio H Lee MJ 2009 HnRNP C1 C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1 The Kobe Journal of Medical Sciences 54 5 E227 36 PMID 19628962 Yong J Wan L Dreyfuss G May 2004 Why do cells need an assembly machine for RNA protein complexes Trends in Cell Biology 14 5 226 32 doi 10 1016 j tcb 2004 03 010 PMID 15130578 Chen HH Chang JG Lu RM Peng TY Tarn WY November 2008 The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 SMN2 gene Molecular and Cellular Biology 28 22 6929 38 doi 10 1128 MCB 01332 08 PMC 2573304 PMID 18794368 Cogulu O Durmaz B Pehlivan S Alpman A Ozkinay F June 2009 Evaluation of the SMN and NAIP genes in a family homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy Genetic Testing and Molecular Biomarkers 13 3 287 8 doi 10 1089 gtmb 2008 0139 PMID 19397406 This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title SMN2 amp oldid 1116592290, wikipedia, wiki, book, books, library,
