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Contribution to Book
Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes
RNA Metabolism in Neurodegenerative Diseases
  • Ravindra N. Singh, Iowa State University
  • Natalia N. Singh, Iowa State University
Document Type
Book Chapter
Publication Version
Accepted Manuscript
Publication Date

Spinal muscular atrophy (SMA) is one of the major genetic disorders associated with infant mortality. More than 90% cases of SMA result from deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, does not compensate for the loss of SMN1due to predominant skipping of exon 7. However, correction of SMN2 exon 7 splicing has proven to confer therapeutic benefits in SMA patients. The only approved drug for SMA is an antisense oligonucleotide (Spinraza™/Nusinersen), which corrects SMN2 exon 7 splicing by blocking intronic splicing silencer N1 (ISS-N1) located immediately downstream of exon 7. ISS-N1 is a complex regulatory element encompassing overlapping negative motifs and sequestering a cryptic splice site. More than 40 protein factors have been implicated in the regulation of SMN exon 7 splicing. There is evidence to support that multiple exons of SMN are alternatively spliced during oxidative stress, which is associated with a growing number of pathological conditions. Here, we provide the most up to date account of the mechanism of splicing regulation of the SMN genes.


This is a post-peer-review, pre-copyedit version of a book chapter published as Singh R.N., Singh N.N. "Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes." In Sattler R., Donnelly C. (eds.) RNA Metabolism in Neurodegenerative Diseases. Advances in Neurobiology, vol. 20. Springer, Cham (2018): 31-61. The final authenticated version is available online at DOI: 10.1007/978-3-319-89689-2_2. Posted with permission.

Copyright Owner
Springer International Publishing AG
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Citation Information
Ravindra N. Singh and Natalia N. Singh. "Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes" RNA Metabolism in Neurodegenerative Diseases Vol. 20 (2018) p. 31 - 61
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