Novel isoforms of adhesion G protein coupled receptor B1 (ADGRB1/BAI1)
generated from an alternative promoter in intron 17
Abstract
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 gene. Two major types of mRNAs were identified in
human and mouse brain, those with a start codon in exon 2 encoding a
full-length protein of a predicted size of 173.5 kDa and shorter
transcripts starting from alternative exons at the intron 17/exon 18
boundary with new or exon 19 start codons, predicting shorter isoforms
of 76.9 and 70.8 kDa, respectively. Immunoblots on wild-type and Adgrb1
exon 2-deleted mice, reverse transcription PCR and promoter-luciferase
reporters 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,
except that the latter exhibits a 19 amino acid extracellular stalk that
can serve as a receptor agonist. Further studies are warranted to
compare the functions of these isoforms and examine the distinct roles
they play in different tissues and cell types.