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Identification of differentially expressed three novel transcript variants of mouse ARNT gene
Author(s) -
Ishqi Hassan Mubarak,
Ur Rehman Sayeed,
Sarwar Tarique,
Husain Mohammed Amir,
Tabish Mohammad
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1464
Subject(s) - gene , identification (biology) , biology , aryl hydrocarbon receptor nuclear translocator , genetics , gene expression , microbiology and biotechnology , computational biology , transcription factor , aryl hydrocarbon receptor , botany
The aryl hydrocarbon receptor nuclear translocator (ARNT/HIF1‐β) is an obligatory transcriptional partner of the aryl hydrocarbon receptor (AHR) and hypoxia‐inducible factor‐1α (HIF‐1α). It has a basic helix‐loop‐helix domain that belongs to period‐ARNT‐single‐minded (PAS) protein family. PAS proteins act as heterodimeric transcription factors with ARNT being master dimerization partner. The ARNT‐HIF‐1α complex is an important transcriptional regulator of the hypoxic response of the tumor cells. Previous studies have reported two transcript variants of the gene produced by alternative splicing in mouse. One transcript variant contains all 22 exons while the other variant lacks exon‐E5. In our study, using combinatorial approach comprising bioinformatics tools and molecular biology techniques involving RT‐PCR, semi‐nested PCR, sequencing and qPCR, we have identified three novel transcript variants of Arnt gene in mouse. All three new transcripts arise as a result of alternative splicing of newly identified exons with exon‐E2, replacing reported exon‐E1. These transcripts encode for three protein isofoms having different N‐termini. The expression of these transcripts was found to be different in different tissues of adult mice. In silico analysis of the upstream region of the new exons revealed three distinct promoter regions designated as PA, PB and PC present upstream of newly identified exons. These promoters possess potential signature sequences for common as well as different transcription factors suggesting complex regulation of Arnt gene. In silico post translational studies of the conceptually translated amino acid sequences of these transcripts show similarity in some of the properties while differ in others. The diversity at N‐termini of protein isoforms suggests the possibility of forming different complexes in different tissues and may also be important for unique interactions with partner molecules. © 2015 IUBMB Life, 68(2):122–135, 2016