IMR Press / FBL / Volume 15 / Issue 3 / DOI: 10.2741/3670

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Splicing of the Survival Motor Neuron genes and implications for treatment of SMA

Show Less
1 The Molecular, Cellular, and Developmental Biology (MCDB) Graduate Program, The Ohio State University, USA
2 The Integrated Biomedical Science Graduate Program (IBGP), The Ohio State University, USA
3 The Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA

These authors contributed equally.

Front. Biosci. (Landmark Ed) 2010, 15(3), 1191–1204; https://doi.org/10.2741/3670
Published: 1 June 2010
Abstract

Proximal spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of the survival motor neuron (SMN) protein. The reduced SMN levels are due to loss of the survival motor neuron-1 (SMN1) gene. Humans carry a nearly identical SMN2 gene that generates a truncated protein, due to a C to T nucleotide alteration in exon 7 that leads to inefficient RNA splicing of exon 7. This exclusion of SMN exon 7 is central to the onset of the SMA disease, however, this offers a unique therapeutic intervention in which corrective splicing of the SMN2 gene would restore SMN function. Exon 7 splicing is regulated by a number of exonic and intronic splicing regulatory sequences and trans-factors that bind them. A better understanding of the way SMN pre-mRNA is spliced has lead to the development of targeted therapies aimed at correcting SMN2 splicing. As therapeutics targeted toward correction of SMN2 splicing continue to be developed available SMA mouse models can be utilized in validating their potential in disease treatment.

Share
Back to top