Warnakulasuriyarachchi D, Ungureanu N H, Holcík M
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.
Cell Death Differ. 2003 Aug;10(8):899-904. doi: 10.1038/sj.cdd.4401256.
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.
HIAP2是一种多功能蛋白，在细胞存活和凋亡的调控中起关键作用。在此，我们表明HIAP2 5'非翻译区作为一种强大的翻译抑制剂发挥作用。对人、小鼠和大鼠序列的分析表明，在HIAP2编码序列上游存在一个短开放阅读框（ORF）。该上游开放阅读框（uORF）的翻译在体内严重抑制下游报告基因的翻译，但在体外则不然。破坏uORF的CUG起始密码子的点突变显著增强了报告基因的翻译，而不影响mRNA水平。我们的结果确定了一种控制HIAP2表达的新型翻译调控机制，并指出了严格调控抗凋亡基因表达的重要性。
