MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK.
Mamm Genome. 2012 Aug;23(7-8):404-15. doi: 10.1007/s00335-012-9398-y. Epub 2012 Apr 27.
C16orf35 is a conserved and widely expressed gene lying adjacent to the human α-globin cluster in all vertebrate species. In-depth sequence analysis shows that C16orf35 (now called NPRL3) is an orthologue of the yeast gene Npr3 (nitrogen permease regulator 3) and, furthermore, is a paralogue of its protein partner Npr2. The yeast Npr2/3 dimeric protein complex senses amino acid starvation and appropriately adjusts cell metabolism via the TOR pathway. Here we have analysed a mouse model in which expression of Nprl3 has been abolished using homologous recombination. The predominant effect on RNA expression appears to involve genes that regulate protein synthesis and cell cycle, consistent with perturbation of the mTOR pathway. Embryos homozygous for this mutation die towards the end of gestation with a range of cardiovascular defects, including outflow tract abnormalities and ventriculoseptal defects consistent with previous observations, showing that perturbation of the mTOR pathway may affect development of the myocardium. NPRL3 is a candidate gene for harbouring mutations in individuals with developmental abnormalities of the cardiovascular system.
C16orf35 是一个保守且广泛表达的基因，位于所有脊椎动物的人类α-球蛋白簇的旁边。深入的序列分析表明，C16orf35（现在称为 NPRL3）是酵母基因 Npr3（氮渗透调节因子 3）的直系同源物，并且是其蛋白伴侣 Npr2 的旁系同源物。酵母 Npr2/3 二聚体蛋白复合物感知氨基酸饥饿，并通过 TOR 途径适当调整细胞代谢。在这里，我们使用同源重组分析了一种 Nprl3 表达被消除的小鼠模型。对 RNA 表达的主要影响似乎涉及调节蛋白质合成和细胞周期的基因，这与 mTOR 途径的干扰一致。这种突变的纯合子胚胎在妊娠末期死亡，伴有一系列心血管缺陷，包括流出道异常和室间隔缺损，与之前的观察结果一致，表明 mTOR 途径的干扰可能影响心肌的发育。NPRL3 是携带心血管系统发育异常个体突变的候选基因。
