Comparative genomic sequence analysis and isolation of human and mouse alternative EGFR transcripts encoding...

Area of Science:

• Genomics
• Molecular Biology
• Cell Biology

Background:

• The epidermal growth factor receptor (EGFR) is a crucial cell surface receptor involved in various biological processes.
• Understanding the genomic organization and alternative splicing of EGFR is essential for comprehending its function and dysregulation.

Purpose of the Study:

• To present the annotated genomic sequence and exon-intron organization of the human and mouse EGFR genes.
• To identify and characterize alternative EGFR transcripts and their encoded protein isoforms.
• To investigate the mechanisms generating alternative EGFR transcripts and their evolutionary conservation.

Main Methods:

• Computational analysis of genomic sequences.
• Experimental validation of transcript identification.
• Analysis of gene structure, including exon-intron boundaries.
• Comparative analysis across species.

Main Results:

• The human and mouse EGFR genes span approximately 200 kb and are encoded by 28 exons.
• Four alternative EGFR transcripts (two human, two mouse) of 2.4-3.0 kb were identified.
• Truncated EGFR isoforms (110-kDa) containing only the ligand-binding domain were encoded by specific alternative transcripts.
• An aberrant EGFR transcript in A431 cells resulted from splicing to a recombinant exon due to chromosomal translocation.
• Alternative EGFR transcripts in human, mouse, rat, and chicken exhibit distinct splicing and non-conserved 3' sequences.

Conclusions:

• The EGFR gene exhibits complex alternative splicing, generating truncated receptor isoforms.
• These truncated isoforms, found across diverse species, may possess significant functional roles in regulating EGFR signaling.
• The aberrant transcript in A431 cells highlights the potential for genomic rearrangements to create novel EGFR variants.