Hahnewald Rita, Leimkühler Silke, Vilaseca Antonia, Acquaviva-Bourdain Cecile, Lenz Ulrike, Reiss Jochen
Institut für Humangenetik der Universität Göttingen, Heinrich-Düker-Weg 12, 37073 Göttingen, Germany.
Mol Genet Metab. 2006 Nov;89(3):210-3. doi: 10.1016/j.ymgme.2006.04.008. Epub 2006 Jun 5.
The small and large subunits of molybdopterin (MPT) synthase (MOCS2A and MOCS2B), are both encoded by the MOCS2 gene in overlapping and shifted open reading frames (ORFs), which is a highly unusual structure for eukaryotes. Theoretical analysis of genomic sequences suggested that the expression of these overlapping ORFs is facilitated by the use of alternate first exons leading to alternative transcripts. Here, we confirm the existence of these overlapping transcripts experimentally. Further, we identified a deletion in a molybdenum cofactor deficient patient, which removes the start codon for the small subunit (MOCS2A). We observed undisturbed production of both transcripts, while Western blot analysis demonstrated that MOCS2B, the large subunit, is unstable in the absence of MOCS2A. This reveals new insights into the expression of this evolutionary ancient anabolic system.
钼蝶呤（MPT）合酶的小亚基和大亚基（MOCS2A和MOCS2B）均由MOCS2基因编码，其开放阅读框（ORF）相互重叠且发生了移位，这对于真核生物来说是一种非常不寻常的结构。基因组序列的理论分析表明，这些重叠ORF的表达是通过使用可变的第一个外显子来促进的，从而产生可变转录本。在这里，我们通过实验证实了这些重叠转录本的存在。此外，我们在一名钼辅因子缺乏症患者中发现了一处缺失，该缺失去除了小亚基（MOCS2A）的起始密码子。我们观察到两种转录本的产生均未受干扰，而蛋白质免疫印迹分析表明，在缺乏MOCS2A的情况下，大亚基MOCS2B不稳定。这揭示了对这个进化上古老的合成代谢系统表达的新见解。
