Campus Units
Biomedical Sciences
Document Type
Book Chapter
Publication Version
Accepted Manuscript
Publication Date
2018
Journal or Book Title
RNA Metabolism in Neurodegenerative Diseases
Volume
20
First Page
31
Last Page
61
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.
Copyright Owner
Springer International Publishing AG
Copyright Date
2018
Language
en
File Format
application/pdf
Recommended Citation
Singh, Ravindra N. and Singh, Natalia N., "Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes" (2018). Biomedical Sciences Publications. 65.
https://lib.dr.iastate.edu/bms_pubs/65
Included in
Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Genetic Processes Commons, Genetics Commons
Comments
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.