The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Splicing of a Critical Exon of Human Survival Motor Neuron Is Regulated by a Unique Silencer Element Located in the Last Intron
Open accessAbstract
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. Here we describe a novel inhibitory element located immediately downstream of the 5' splice site in intron 7. We call this element intronic splicing silencer N1 (ISS-N1). Deletion of ISS-N1 promoted exon 7 inclusion in mRNAs derived from the SMN2 minigene. Underlining the dominant role of ISS-N1 in exon 7 skipping, abrogation of a number of positive cis elements was tolerated when ISS-N1 was deleted. Confirming the silencer function of ISS-N1, an antisense oligonucleotide against ISS-N1 restored exon 7 inclusion in mRNAs derived from the SMN2 minigene or from endogenous SMN2. Consistently, this oligonucleotide increased the levels of SMN protein in SMA patient-derived cells that carry only the SMN2 gene. Our findings underscore for the first time the profound impact of an evolutionarily nonconserved intronic element on SMN2 exon 7 splicing. Considering that oligonucleotides annealing to intronic sequences do not interfere with exon-junction complex formation or mRNA transport and translation, ISS-N1 provides a very specific and efficient therapeutic target for antisense oligonucleotide-mediated correction of SMN2 splicing in SMA.
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Identification and characterization of a spinal muscular atrophy-determining gene
Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Benichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90460-3 · Cited by 3,990
Mechanisms of Alternative Pre-Messenger RNA Splicing
Black, D. L. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161720 · Cited by 2,704
ESEfinder: a web resource to identify exonic splicing enhancers
Cartegni, L. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg616 · Cited by 1,603
Lorson, C. L., Hahnen, E., Androphy, E. J., & Wirth, B. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6307 · Cited by 1,532
Self-citationPre-mRNA splicing and human disease
Faustino, N. A., & Cooper, T. A. (2003) · Genes & Development · doi:10.1101/gad.1048803 · Cited by 1,256
Correlation between severity and SMN protein level in spinal muscular atrophy
Lefebvre, S., Burlet, P., Liu, Q., Bertrandy, S., Clermont, O., Munnich, A., Dreyfuss, G., & Melki, J. (1997) · Nature Genetics · doi:10.1038/ng0797-265 · Cited by 1,100
Analysis of gene function in somatic mammalian cells using small interfering RNAs
Elbashir, S. (2002) · Methods · doi:10.1016/s1046-2023(02)00023-3 · Cited by 1,095
Sorting out the complexity of SR protein functions
GRAVELEY, B. R. (2000) · RNA · doi:10.1017/s1355838200000960 · Cited by 1,078
Predictive Identification of Exonic Splicing Enhancers in Human Genes
Fairbrother, W. G., Yeh, R.-F., Sharp, P. A., & Burge, C. B. (2002) · Science · doi:10.1126/science.1073774 · Cited by 1,036
Monani, U. R. (1999) · Human Molecular Genetics · doi:10.1093/hmg/8.7.1177 · Cited by 954
Cited by
RNA therapeutics: beyond RNA interference and antisense oligonucleotides
Kole, R., Krainer, A. R., & Altman, S. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3625 · Cited by 1,152
Finkel, R. S., Chiriboga, C. A., Vajsar, J., Day, J. W., Montes, J., De Vivo, D. C., Yamashita, M., Rigo, F., Hung, G., Schneider, E., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31408-8 · Cited by 1,019
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788
Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model
Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M. A., Bennett, C. F., & Krainer, A. R. (2010) · Genes & Development · doi:10.1101/gad.1941310 · Cited by 664
Splice-switching antisense oligonucleotides as therapeutic drugs
Havens, M. A., & Hastings, M. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw533 · Cited by 538
Metadata
- Authors
- Singh, N. K., Singh, N. N., Androphy, E. J., & Singh, R. N.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2006-02-01
- Volume
- 26
- Issue
- 4
- Pages
- 1333-1346
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2152766938
- Cited by
- 454
- References
- 62
- FWCI
- 5.24
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Splicing of a Critical Exon of Human Survival Motor Neuron Is Regulated by a Unique Silencer Element Located in the Last Intron. https://app.cochat.ai/papers/10.1128/mcb.26.4.1333-1346.2006
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- Singh, N. K., Singh, N. N., Androphy, E. J., & Singh, R. N. (2006). Splicing of a Critical Exon of Human Survival Motor Neuron Is Regulated by a Unique Silencer Element Located in the Last Intron. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.26.4.1333-1346.2006
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