Regulation of the expression of the oncogene EVI1 through the use of alternative mRNA 5'-ends.
The EVI1 gene plays important roles in development and leukemogenesis. Recently, human EVI1 has been shown to give rise to at least six different mRNA variants with alternative 5'-ends, only some of which are conserved in mice. In order to gain a basic understanding of the regulation and potential biological importance of these alternative transcripts, we confirmed their expression by Northern blot, and, using real time quantitative RT-PCR, compared their abundance and stability under different conditions. The general expression patterns of the EVI1 5'-end variants in a panel of 20 human tissues were similar, but particularly high or low levels of some of them were noted in certain tissues. Pronounced differences in the expression of the 5'-end variants were noted in response to all-trans retinoic acid: in a human teratocarcinoma cell line, only the EVI1 transcript variants containing alternative exons 1a and 1b were upregulated in response to this agent. This induction required transcriptional activity of RNA polymerase, but was also associated with a substantial increase in the stability of these mRNA variants.
Aytekin
Metin
M
KIMCL, Abteilung fuer Humangenetik, Medizinische Universitaet Wien, Waehringerstr. 10, A-1090 Wien, Austria.
Vinatzer
Ursula
U
Musteanu
Monica
M
Raynaud
Sophie
S
Wieser
Rotraud
R
D017398:Alternative Splicing; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D011519:Proto-Oncogenes / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin