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Biomedical Sciences

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Publication Version

Accepted Manuscript

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Journal or Book Title

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms




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.


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.

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Elsevier B.V.



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Published Version