Novel Isoforms of Adhesion G Protein-Coupled Receptor B1 (ADGRB1/BAI1) Generated from an Alternative Promoter in Intron 17.

Mol Neurobiol

Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, Heersink School of Medicine, University of Alabama at Birmingham (UAB), WTI 520E, 1824 6th Avenue South, Birmingham, AL, 35233, USA.

Published: June 2024

Brain-specific angiogenesis inhibitor 1 (BAI1) belongs to the adhesion G-protein-coupled receptors, which exhibit large multi-domain extracellular N termini that mediate cell-cell and cell-matrix interactions. To explore the existence of BAI1 isoforms, we queried genomic datasets for markers of active chromatin and new transcript variants in the ADGRB1 (adhesion G-protein-coupled receptor B1) gene. Two major types of mRNAs were identified in human/mouse brain, those with a start codon in exon 2 encoding a full-length protein of a predicted size of 173.5/173.3 kDa and shorter transcripts starting from alternative exons at the intron 17/exon 18 boundary with new or exon 19 start codons, predicting two shorter isoforms of 76.9/76.4 and 70.8/70.5 kDa, respectively. Immunoblots on wild-type and Adgrb1 exon 2-deleted mice, reverse transcription PCR, and promoter-luciferase reporter assay confirmed that the shorter isoforms originate from an alternative promoter in intron 17. The shorter BAI1 isoforms lack most of the N terminus and are very close in structure to the truncated BAI1 isoform generated through GPS processing from the full-length receptor. The cleaved BAI1 isoform has a 19 amino acid extracellular stalk that may serve as a receptor agonist, while the alternative transcripts generate BAI1 isoforms with extracellular N termini of 5 or 60 amino acids. Further studies are warranted to compare the functions of these isoforms and examine the distinct roles they play in different tissues and cell types.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-024-04293-3DOI Listing

Publication Analysis

Top Keywords

bai1 isoforms
12
alternative promoter
8
promoter intron
8
adhesion g-protein-coupled
8
extracellular termini
8
shorter isoforms
8
bai1 isoform
8
bai1
6
isoforms
6
novel isoforms
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!