Modulation of transcriptional activity in brain lower grade glioma by alternative splicing

PeerJ
Jin LiHong Liang

Abstract

Proteins that modify the activity of transcription factors (TFs) are often called modulators and play a vital role in gene transcriptional regulation. Alternative splicing is a critical step of gene processing, and differentially spliced isoforms may have different functions. Alternative splicing can modulate gene function by adding or removing certain protein domains and thereby influence the activity of a protein. The objective of this study is to investigate the role of alternative splicing in modulating the transcriptional regulation in brain lower grade glioma (LGG), especially transcription factor ELK1, which is closely related to various disorders, including Alzheimer's disease and Down syndrome. The results showed that changes in the exon inclusion ratio of proteins APP and STK16 are associated with changes in the expression correlation between ELK1 and its targets. In addition, the structural features of the two modulators are strongly associated with the pathological impact of exon inclusion. The results of our analysis suggest that alternatively spliced proteins have different functions in modifying transcription factors and can thereby induce the dysregulation of multiple genes.

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Citations

Apr 13, 2019·International Journal of Molecular Sciences·Junjun WangXin Zhang

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Methods Mentioned

BETA
RNA-Seq

Software Mentioned

GEM
IPA ( Ingenuity Pathway Analysis )
STAR aligner
NGSUtils
DAVID
R
ExonImpact

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