Campus Units

Biomedical Sciences

Document Type

Article

Publication Version

Published Version

Publication Date

11-2017

Journal or Book Title

Frontiers in Microbiology

Volume

8

First Page

2252

DOI

10.3389/fmicb.2017.02252

Abstract

Humans carry two nearly identical copies of Survival Motor Neuron gene: SMN1 and SMN2. Mutations or deletions of SMN1, which codes for SMN, cause spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. Aberrant expression or localization of SMN has been also implicated in other pathological conditions, including male infertility, inclusion body myositis, amyotrophic lateral sclerosis and osteoarthritis. SMN2 fails to compensate for the loss of SMN1 due to skipping of exon 7, leading to the production of SMNΔ7, an unstable protein. In addition, SMNΔ7 is less functional due to the lack of a critical C-terminus of the full-length SMN, a multifunctional protein. Alu elements are specific to primates and are generally found within protein coding genes. About 41% of the human SMN gene including promoter region is occupied by more than 60 Alu-like sequences. Here we discuss how such an abundance of Alu-like sequences may contribute toward SMA pathogenesis. We describe the likely impact of Alu elements on expression of SMN. We have recently identified a novel exon 6B, created by exonization of an Alu-element located within SMN intron 6. Irrespective of the exon 7 inclusion or skipping, transcripts harboring exon 6B code for the same SMN6B protein that has altered C-terminus compared to the full-length SMN. We have demonstrated that SMN6B is more stable than SMNΔ7 and likely functions similarly to the full-length SMN. We discuss the possible mechanism(s) of regulation of SMN exon 6B splicing and potential consequences of the generation of exon 6B-containing transcripts.

Comments

This article is published as Ottesen, Eric W., Joonbae Seo, Natalia N. Singh, and Ravindra N. Singh. "A multilayered control of the human Survival Motor Neuron gene expression by Alu elements." Frontiers in Microbiology 8 (2017): 2252. doi: 10.3389/fmicb.2017.02252. Posted with permission.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

Ottesen, Seo, Singh and Singh

Language

en

File Format

application/pdf

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