The translation of an antiapoptotic protein HIAP2 is regulated by an upstream open reading frame.
HIAP2 is a multifunctional protein that is critically involved in the regulation of cell survival and apoptosis. Here, we show that HIAP2 5' untranslated region functions as a strong inhibitor of translation. Sequence analysis of human, mouse and rat sequences revealed that there exists a short open reading frame (ORF) that is located just upstream of the HIAP2 coding sequence. The translation of this uORF severely inhibited translation of the downstream reporter gene in vivo but not in vitro. Point mutation that destroys the CUG initiating codon of uORF markedly enhanced translation of the reporter gene without affecting the mRNA levels. Our results identify a novel translational regulatory mechanism that controls the expression of HIAP2 and point to the importance of tight regulation of antiapoptotic gene expression.
Warnakulasuriyarachchi
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Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario Research Institute and Department of Pediatrics, University of Ottawa, 401 Smyth Road, Ottawa, ON, Canada K1H 8L1.
Ungureanu
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NH
Holcík
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M
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002474:Cell-Free System; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D018387:Codon, Initiator / Q000235:genetics; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D016366:Open Reading Frames / Q000235:genetics* / Q000502:physiology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; D001616:beta-Galactosidase