A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells.
Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor-specific products that provide tumor cells with a growth and/or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5' exons of the JAZF1 gene on chromosome 7p15 to 3' exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti-apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans-splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro-neoplastic owing to constitutive expression of chimeric gene products normally generated by trans-splicing of RNAs in developing tissues.
Li
Hui
H
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Wang
Jinglan
J
Mor
Gil
G
Sklar
Jeffrey
J
D015687:Cell Hypoxia; D002460:Cell Line; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D003676:Deferoxamine / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000235:genetics; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005091:Exons; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008597:Menstrual Cycle; D050506:Mutant Chimeric Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D020040:Trans-Splicing; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014178:Translocation, Genetic
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; C430460:JAZF1 protein, human; D050506:Mutant Chimeric Proteins; D009363:Neoplasm Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; C430461:SUZ12 protein, human; D014157:Transcription Factors; D011374:Progesterone; D003676:Deferoxamine