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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
Article
Publication Version
Accepted Manuscript
Publication Date
1-1-2018
DOI
10.1007/978-3-319-89689-2_2
Abstract

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.

Comments

This is a post-peer-review, pre-copyedit version of an article published as Singh R.N., Singh N.N. (2018) "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. The final authenticated version is available online at DOI: 10.1007/978-3-319-89689-2_2. Springer, Cham. Posted with permission.

Copyright Owner
Springer International Publishing AG, part of Springer Nature
Language
en
File Format
application/pdf
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
Available at: http://works.bepress.com/ravindra-singh/36/