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TNF-alpha regulates alternative splicing of genes participating in pathways of crucial metabolic syndromes; a transcriptome wide study.

Authors
  • Louis, Jiss Maria1
  • Vaz, Candida2
  • Balaji, Advait1
  • Tanavde, Vivek3
  • Talukdar, Indrani4
  • 1 Dept. of Biological Sciences, BITS Pilani, K. K. Birla Goa Campus, Zuarinagar, Goa 403726, India. , (India)
  • 2 Bioinformatics Institute, Agency for Science Technology and Research, 30 Biopolis Street, #07-01 Matrix, Singapore 1386713, Singapore. , (Singapore)
  • 3 Bioinformatics Institute, Agency for Science Technology and Research, 30 Biopolis Street, #07-01 Matrix, Singapore 1386713, Singapore; Division of Biological and Life Sciences, School of Arts and Sciences, Ahmedabad University, Navrangpura, Ahmedabad 380009, India. , (India)
  • 4 Dept. of Biological Sciences, BITS Pilani, K. K. Birla Goa Campus, Zuarinagar, Goa 403726, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
Cytokine
Publisher
Elsevier
Publication Date
Jan 01, 2020
Volume
125
Pages
154815–154815
Identifiers
DOI: 10.1016/j.cyto.2019.154815
PMID: 31476685
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

TNF-α, a pro-inflammatory cytokine is one of the major contributors for metabolic syndromes including insulin resistance, obesity, type II diabetes etc. The role of alternative splicing, a post-transcriptional regulation of gene expression on the onset of these syndromes is poorly understood. However, the role of alternative splicing, which more than 95% of all exons in eukaryotic cells undergo in several other diseases including cancer and muscle dystrophy, has been elucidated. In this study we aim to investigate the role of alternative splicing in pathways leading to metabolic syndromes mediated by TNF-α. A genome wide transcriptome analysis was carried out using Illumina platform. Results were validated using RT-PCR analysis. Various bioinformatics tools and databases (for example IPA, KEGG, STRING etc) were used for the pathway and interactome analysis. Transcriptome wide analysis revealed that TNF-α treatment in vitro causes a significant change in expression of 228 genes at the level of alternative splicing. Regulation of some of these genes was validated in different cell lines. Pathway analysis showed at least 15% of the alternatively spliced genes fall under the contributory pathways leading to different metabolic syndromes, among which the maximally interconnected genes were transcription regulators. These findings suggest that TNF-α.-mediated alternative splicing plays a crucial role in regulating various genes involved in pathways connected to metabolic syndromes. Copyright © 2019 Elsevier Ltd. All rights reserved.

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