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Novel isoforms of adhesion G protein coupled receptor B1 (ADGRB1/BAI1) generated from an alternative promoter in intron 17
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  • Rashed Rezwan Parag,
  • Takahiro Yamamoto,
  • Kiyotaka Saito,
  • Erwin Van Meir
Rashed Rezwan Parag
The University of Alabama at Birmingham
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Takahiro Yamamoto
The University of Alabama at Birmingham
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Kiyotaka Saito
Erwin Van Meir
The University of Alabama at Birmingham

Corresponding Author:[email protected]

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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.
20 Apr 2023Submitted to Basic & Clinical Pharmacology & Toxicology
21 Apr 2023Submission Checks Completed
21 Apr 2023Assigned to Editor
21 Apr 2023Review(s) Completed, Editorial Evaluation Pending
24 Apr 2023Reviewer(s) Assigned
30 May 2023Editorial Decision: Revise Minor