A Multilayered Control of the Human Survival Motor Neuron Gene Expression by Alu Elements

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dc.contributor.author Ottesen, Eric
dc.contributor.author Ottesen, Eric
dc.contributor.author Seo, Joonbae
dc.contributor.author Singh, Natalia
dc.contributor.author Singh, Ravindra
dc.contributor.author Singh, Ravindra
dc.contributor.department Biomedical Sciences
dc.date 2018-02-22T06:03:52.000
dc.date.accessioned 2020-06-30T00:53:28Z
dc.date.available 2020-06-30T00:53:28Z
dc.date.copyright Sun Jan 01 00:00:00 UTC 2017
dc.date.issued 2017-11-01
dc.description.abstract <p>Humans carry two nearly identical copies of <em>Survival Motor Neuron</em> gene: <em>SMN1</em> and <em>SMN2.</em> Mutations or deletions of <em>SMN1</em>, 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. <em>SMN2</em> fails to compensate for the loss of <em>SMN1</em> 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 <em>SMN</em> 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 <em>SMN</em> 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 <em>SMN</em> exon 6B splicing and potential consequences of the generation of exon 6B-containing transcripts.</p>
dc.description.comments <p>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." <em>Frontiers in Microbiology</em> 8 (2017): 2252. doi: <a href="https://doi.org/10.3389/fmicb.2017.02252">10.3389/fmicb.2017.02252</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/bms_pubs/56/
dc.identifier.articleid 1052
dc.identifier.contextkey 11606634
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath bms_pubs/56
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/11182
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/bms_pubs/56/2017_RSingh_MultilayeredControl.pdf|||Sat Jan 15 00:57:07 UTC 2022
dc.source.uri 10.3389/fmicb.2017.02252
dc.subject.disciplines Comparative and Laboratory Animal Medicine
dc.subject.disciplines Genetics and Genomics
dc.subject.disciplines Veterinary Microbiology and Immunobiology
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.subject.keywords spinal muscular atrophy
dc.subject.keywords SMA
dc.subject.keywords survival motor neuron
dc.subject.keywords SMN
dc.subject.keywords SMN6B
dc.subject.keywords Alu
dc.subject.keywords exonization
dc.subject.keywords transposable elements
dc.title A Multilayered Control of the Human Survival Motor Neuron Gene Expression by Alu Elements
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 30dd0ac9-28a2-4363-bac0-4f19aa596e2f
relation.isAuthorOfPublication d5765265-0e5d-4de9-8e17-19842ab75544
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
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