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Antisense transcripts at the EMX2 locus in human and mouse
Ferrin C Noonan1, Paul J Goodfellow, Lora J Staloch
1Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
The homeodomain transcription factor EMX2 is critical for central nervous system and urogenital development. In addition, EMX2 maps to a region of allelic deletion corresponding to a putative endometrial tumor suppressor at 10q26. We now report another polyadenylated transcript that is transcribed on the strand opposite to EMX2 and overlaps with the EMX2 transcript. This transcript was designated EMX2OS (OS, opposite strand), and an orthologous transcript present at the murine Emx2 locus was designated Emx2os. Alternative splicing to generate transcripts with varying 5' sequences was detected in the human but not the mouse. Neither ortholog contains a significant open reading frame, nor is primary sequence conserved between the two species. The sense and antisense transcripts display coordinate expression in that EMX2 and EMX2OS are abundant in normal postmenopausal endometrium, reduced in premenopausal endometrium, and absent or reduced in a majority of primary endometrial tumors. EMX2, EMX2OS, Emx2, and Emx2os are abundant in the uterine endometrium, with sense and antisense transcripts exhibiting identical expression patterns. Conservation of functional human and murine EMX2 antisense genes, of overlap between the sense and the antisense transcripts, and of identical cellular expression patterns suggests a biological function for EMX2OS, presumably to regulate EMX2.
Insights
A newly discovered EMX2 opposite strand (EMX2OS) transcript shares expression patterns with EMX2 in the endometrium. Both are reduced in tumors, suggesting a potential role for EMX2OS in endometrial cancer suppression.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The homeodomain transcription factor EMX2 is crucial for development.
- EMX2 is located at 10q26, a region associated with endometrial tumor suppressor activity.
- A novel antisense transcript, EMX2OS, has been identified.
- EMX2OS is transcribed from the opposite strand of EMX2 and overlaps its locus.
Purpose of the Study:
- To characterize the novel EMX2OS transcript.
- To investigate the expression patterns of EMX2 and EMX2OS in endometrial tissues.
- To explore the potential functional relationship between EMX2 and EMX2OS.
Main Methods:
- Transcript identification and characterization.
- Analysis of alternative splicing in human and mouse orthologs.
- Quantitative expression analysis of EMX2 and EMX2OS in normal and cancerous endometrial tissues.
- Comparative analysis of human and murine orthologs.
Main Results:
- A novel antisense transcript, EMX2OS, was identified, with an ortholog Emx2os in mice.
- EMX2OS exhibits alternative splicing in humans but not mice.
- Neither EMX2OS nor Emx2os has a significant open reading frame, and primary sequence is not conserved.
- EMX2 and EMX2OS show coordinate expression in the endometrium, abundant in postmenopausal, reduced in premenopausal, and absent/reduced in tumors.
- Identical expression patterns were observed for EMX2, EMX2OS, Emx2, and Emx2os in the uterine endometrium.
Conclusions:
- The conservation of EMX2OS and its coordinate expression with EMX2 suggests a biological function.
- EMX2OS likely plays a role in regulating EMX2.
- The shared expression pattern and reduction in endometrial tumors indicate a potential tumor suppressor role for the EMX2/EMX2OS axis.
