Silva Iris A L, Varela Débora, Cancela M Leonor, Conceição Natércia
PhD program in Biomedical Sciences, Faculty of Medicine and Biomedical Sciences, University of Algarve, Faro 8005-139, Portugal.
Centre of Marine Sciences (CCMAR), University of Algarve, Faro 8005-139, Portugal.
Genome. 2022 Oct 1;65(10):513-523. doi: 10.1139/gen-2022-0019. Epub 2022 Aug 29.
Optineurin (OPTN) is involved in a variety of mechanisms, such as autophagy, vesicle trafficking, and nuclear factor kappa-B (NF-κB) signaling. Mutations in the gene have been associated with different pathologies, including glaucoma, amyotrophic lateral sclerosis, and Paget's disease of bone. Since the relationship between fish and mammalian OPTN is not well understood, the objective of the present work was to characterize the zebrafish gene and protein structure and to investigate its transcriptional regulation. Through a comparative in silico analysis, we observed that zebrafish presents genomic features similar to those of its human counterpart, including its neighboring genes and structure. A comparison of OPTN protein from different species revealed a high degree of conservation in its functional domains and three-dimensional structure. Furthermore, our in vitro transient-reporter analysis identified a functional promoter in the upstream region of the zebrafish gene, along with a region important for its transcription regulation. Site-directed mutagenesis revealed that the NF-κB motif is responsible for the activation of this region. In conclusion, with this study, we characterize zebrafish and our results indicate that zebrafish can be considered as an alternative model to study OPTN's biological role in bone-related diseases.
视神经病相关蛋白（OPTN）参与多种机制，如自噬、囊泡运输和核因子κB（NF-κB）信号传导。该基因的突变与不同的病理状况相关，包括青光眼、肌萎缩侧索硬化症和骨佩吉特病。由于鱼类和哺乳动物的OPTN之间的关系尚未完全了解，本研究的目的是表征斑马鱼的基因和蛋白质结构，并研究其转录调控。通过比较性的计算机分析，我们观察到斑马鱼的基因组特征与其人类对应物相似，包括其相邻基因和结构。不同物种的OPTN蛋白比较显示其功能域和三维结构具有高度保守性。此外，我们的体外瞬时报告基因分析在斑马鱼基因的上游区域鉴定出一个功能性启动子，以及一个对其转录调控很重要的区域。定点诱变表明NF-κB基序负责该区域的激活。总之，通过本研究，我们表征了斑马鱼的OPTN，我们的结果表明斑马鱼可被视为研究OPTN在骨相关疾病中的生物学作用的替代模型。
