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Article
A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein
Scientific Reports
  • Joonbae Seo, Iowa State University
  • Natalia N. Singh, Iowa State University
  • Eric W. Ottesen, Iowa State University
  • Brian M. Lee, Iowa State University
  • Ravindra N. Singh, Iowa State University
Document Type
Article
Publication Version
Published Version
Publication Date
1-1-2016
DOI
10.1038/srep30778
Abstract
Spinal muscular atrophy (SMA), a leading genetic disease of children and infants, is caused by mutations or deletions of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to skipping of exon 7. SMN2predominantly produces SMNΔ7, an unstable protein. Here we report exon 6B, a novel exon, generated by exonization of an intronic Alu-like sequence of SMN. We validate the expression of exon 6B-containing transcripts SMN6B and SMN6BΔ7 in human tissues and cell lines. We confirm generation of SMN6B transcripts from both SMN1 and SMN2. We detect expression of SMN6B protein using antibodies raised against a unique polypeptide encoded by exon 6B. We analyze RNA-Seq data to show that hnRNP C is a potential regulator of SMN6B expression and demonstrate that SMN6B is a substrate of nonsense-mediated decay. We show interaction of SMN6B with Gemin2, a critical SMN-interacting protein. We demonstrate that SMN6B is more stable than SMNΔ7 and localizes to both the nucleus and the cytoplasm. Our finding expands the diversity of transcripts generated from human SMN genes and reveals a novel protein isoform predicted to be stably expressed during conditions of stress.
Comments

This article is published as Seo, Joonbae, Natalia N. Singh, Eric W. Ottesen, Brian M. Lee, and Ravindra N. Singh. "A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein." Scientific reports 6 (2016), doi: 10.1038/srep30778. Posted with permission.

Creative Commons License
Creative Commons Attribution 4.0
Copyright Owner
The Authors
Language
en
File Format
application/pdf
Citation Information
Joonbae Seo, Natalia N. Singh, Eric W. Ottesen, Brian M. Lee, et al.. "A novel human-specific splice isoform alters the critical C-terminus of Survival Motor Neuron protein" Scientific Reports Vol. 6 (2016) p. 30778
Available at: http://works.bepress.com/eric-ottesen/4/