Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
Biol Chem. 2013 Jun;394(6):753-60. doi: 10.1515/hsz-2012-0309.
Cyclooxygenase 1b (COX-1b) is a splice variant of COX-1, containing a retained intron 1 within the signal peptide sequence. COX-1b mRNA is found in many species, but the existence of a functionally active protein, which is possibly related to different species-dependent lengths of intron 1, is controversially discussed. The human intron 1 comprises 94 bp, and the resulting frameshift at the intron 1-exon 2 junction creates a premature stop codon. Nevertheless, full-length human COX-1b protein expression, including translated intron 1 and the signal peptide, has been reported and was explained by a frameshift repair. In this study, the fate of COX-1b mRNA in a human overexpression system is analyzed. Independent of the hypothetical frameshift repair mechanism, the splicing of the COX-1b intron 1, resulting in COX-1 mRNA and removal of the signal peptide during protein maturation, with subsequent generation of a COX-1 protein is demonstrated.
环氧化酶 1b（COX-1b）是 COX-1 的剪接变异体，在信号肽序列内包含一个保留的内含子 1。COX-1b mRNA 存在于许多物种中，但关于是否存在具有功能活性的蛋白质存在争议，这可能与不同物种内含子 1 的长度有关。人类内含子 1 包含 94 个碱基对，在内含子 1-外显子 2 连接处产生的移码导致过早的终止密码子。然而，已报道并通过移码修复解释了全长人类 COX-1b 蛋白的表达，包括翻译的内含子 1 和信号肽。在本研究中，分析了 COX-1b mRNA 在人过表达系统中的命运。独立于假设的移码修复机制，在蛋白质成熟过程中，COX-1b 内含子 1 的剪接导致 COX-1 mRNA 和信号肽的去除，随后生成 COX-1 蛋白。
