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The genomic structure of the human UFO receptor
A S Schulz1, L Schleithoff, M Faust
1Department of Pediatrics II, University of Ulm, Germany.
Abstract:
Using a DNA transfection-tumorigenicity assay we have recently identified the UFO oncogene. It encodes a tyrosine kinase receptor characterized by the juxtaposition of two immunoglobulin-like and two fibronectin type III repeats in its extracellular domain. Here we describe the genomic organization of the human UFO locus. The UFO receptor is encoded by 20 exons that are distributed over a region of 44 kb. Different isoforms of UFO mRNA are generated by alternative splicing of exon 10 and differential usage of two imperfect polyadenylation sites resulting in the presence or absence of 1.5-kb 3' untranslated sequences. Primer extension and S1 nuclease analyses revealed multiple transcriptional initiation sites including a major site 169 bp upstream of the translation start site. The promoter region is GC rich, lacks TATA and CAAT boxes, but contains potential recognition sites for a variety of trans-acting factors, including Sp1, AP-2 and the cyclic AMP response element-binding protein. Proto-UFO and its oncogenic counterpart exhibit identical cDNA and promoter regions sequences. Possible modes of UFO activation are discussed.
Insights
The UFO oncogene encodes a tyrosine kinase receptor. Its genomic organization and alternative splicing generate diverse mRNA isoforms, influencing oncogenic potential.
Area of Science:
- Molecular Biology
- Genomics
- Oncology
Background:
- The UFO oncogene was recently identified using a DNA transfection-tumorigenicity assay.
- The UFO gene encodes a tyrosine kinase receptor with specific extracellular domain features.
Purpose of the Study:
- To describe the genomic organization of the human UFO locus.
- To investigate the mechanisms of UFO mRNA isoform generation and transcriptional regulation.
Main Methods:
- DNA transfection-tumorigenicity assay
- Analysis of genomic organization (exon/intron structure)
- Alternative splicing analysis (mRNA isoforms)
- Transcriptional initiation site mapping (primer extension, S1 nuclease)
- Promoter region analysis
Main Results:
- The human UFO locus spans 44 kb and is organized into 20 exons.
- Alternative splicing of exon 10 and differential polyadenylation generate distinct UFO mRNA isoforms.
- Multiple transcriptional initiation sites were identified, with a major site upstream of the translation start.
- The promoter region is GC-rich, lacks TATA/CAAT boxes, and contains binding sites for transcription factors like Sp1 and AP-2.
- Proto-UFO and its oncogenic counterpart share identical cDNA and promoter sequences.
Conclusions:
- The genomic structure of UFO supports the generation of diverse mRNA isoforms through alternative splicing and polyadenylation.
- The identified promoter elements suggest complex transcriptional regulation of the UFO gene.
- The identical cDNA and promoter sequences between proto-UFO and oncogenic UFO imply that activation mechanisms may involve regulatory elements outside these regions.