Next Article in Journal
Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer
Previous Article in Journal
Liver Effects of Clinical Drugs Differentiated in Human Liver Slices
Previous Article in Special Issue
Alternative Splicing of hTERT Pre-mRNA: A Potential Strategy for the Regulation of Telomerase Activity
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 576; doi:10.3390/ijms18030576

The Characterization of GSDMB Splicing and Backsplicing Profiles Identifies Novel Isoforms and a Circular RNA That Are Dysregulated in Multiple Sclerosis

1
Department of Biomedical Sciences, Humanitas University, Via Manzoni 113, 20089 Rozzano, Milan, Italy
2
Humanitas Clinical and Research Center, Via Manzoni 56, 20089 Rozzano, Milan, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Akila Mayeda
Received: 29 December 2016 / Revised: 20 February 2017 / Accepted: 1 March 2017 / Published: 7 March 2017
(This article belongs to the Special Issue Pre-mRNA Splicing 2016)
View Full-Text   |   Download PDF [1499 KB, uploaded 7 March 2017]   |  

Abstract

Abnormalities in alternative splicing (AS) are emerging as recurrent features in autoimmune diseases (AIDs). In particular, a growing body of evidence suggests the existence of a pathogenic association between a generalized defect in splicing regulatory genes and multiple sclerosis (MS). Moreover, several studies have documented an unbalance in alternatively-spliced isoforms in MS patients possibly contributing to the disease etiology. In this work, using a combination of PCR-based techniques (reverse-transcription (RT)-PCR, fluorescent-competitive, real-time, and digital RT-PCR assays), we investigated the alternatively-spliced gene encoding Gasdermin B, GSDMB, which was repeatedly associated with susceptibility to asthma and AIDs. The in-depth characterization of GSDMB AS and backsplicing profiles led us to the identification of an exonic circular RNA (ecircRNA) as well as of novel GSDMB in-frame and out-of-frame isoforms. The non-productive splicing variants were shown to be downregulated by the nonsense-mediated mRNA decay (NMD) in human cell lines, suggesting that GSDMB levels are significantly modulated by NMD. Importantly, both AS isoforms and the identified ecircRNA were significantly dysregulated in peripheral blood mononuclear cells of relapsing-remitting MS patients compared to controls, further supporting the notion that aberrant RNA metabolism is a characteristic feature of the disease. View Full-Text
Keywords: GSDMB; alternative splicing; nonsense-mediated mRNA decay; circRNA; multiple sclerosis GSDMB; alternative splicing; nonsense-mediated mRNA decay; circRNA; multiple sclerosis
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Cardamone, G.; Paraboschi, E.M.; Rimoldi, V.; Duga, S.; Soldà, G.; Asselta, R. The Characterization of GSDMB Splicing and Backsplicing Profiles Identifies Novel Isoforms and a Circular RNA That Are Dysregulated in Multiple Sclerosis. Int. J. Mol. Sci. 2017, 18, 576.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top