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Article
How RNA structure dictates the usage of a critical exon of spinal muscular atrophy gene
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
  • Natalia N. Singh, Iowa State University
  • Ravindra N. Singh, Iowa State University
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
7-16-2019
DOI
10.1016/j.bbagrm.2019.07.004
Abstract

Role of RNA structure in pre-mRNA splicing has been implicated for several critical exons associated with genetic disorders. However, much of the structural studies linked to pre-mRNA splicing regulation are limited to terminal stem-loop structures (hairpins) sequestering splice sites. In few instances, role of long-distance interactions is implicated as the major determinant of splicing regulation. With the recent surge of reports of circular RNA (circRNAs) generated by backsplicing, role of Alu-associated RNA structures formed by long-range interactions are taking central stage. Humans contain two nearly identical copies of Survival Motor Neuron (SMN) genes, SMN1 and SMN2. Deletion or mutation of SMN1 coupled with the inability of SMN2 to compensate for the loss of SMN1 due to exon 7 skipping causes spinal muscular atrophy (SMA), one of the leading genetic diseases of children. In this review, we describe how structural elements formed by both local and long-distance interactions are being exploited to modulate SMN2 exon 7 splicing as a potential therapy for SMA. We also discuss how Alu-associated secondary structure modulates generation of a vast repertoire of SMN circRNAs. This article is part of a Special Issue entitled: RNA structure and splicing regulation edited by Francisco Baralle, Ravindra Singh and Stefan Stamm.

Comments

This article is published as Singh, Natalia N., and Ravindra N. Singh. "How RNA structure dictates the usage of a critical exon of spinal muscular atrophy gene." Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms (2019). DOI: 10.1016/j.bbagrm.2019.07.004. Posted with permission.

Creative Commons License
Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International
Copyright Owner
Elsevier B.V.
Language
en
File Format
application/pdf
Citation Information
Natalia N. Singh and Ravindra N. Singh. "How RNA structure dictates the usage of a critical exon of spinal muscular atrophy gene" Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms (2019)
Available at: http://works.bepress.com/ravindra-singh/38/