Iris A L Silva, Débora Varela, M Leonor Cancela, Natércia Conceição
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引用次数: 0
Abstract
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 OPTN 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 optn gene and protein structure and to investigate its transcriptional regulation. Through a comparative in silico analysis, we observed that zebrafish optn 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 optn 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 optn and our results indicate that zebrafish can be considered as an alternative model to study OPTN's biological role in bone-related diseases.
OPTN参与多种机制,如自噬、囊泡运输和核因子κ b (NF-κB)信号传导。OPTN基因的突变与不同的病理有关,包括青光眼、肌萎缩性侧索硬化症和骨佩吉特病。由于鱼类和哺乳动物OPTN之间的关系尚不清楚,本研究的目的是表征斑马鱼的OPTN基因和蛋白结构,并研究其转录调控。通过对比分析,我们观察到斑马鱼的optn具有与人类相似的基因组特征,包括其邻近基因和结构。不同物种的OPTN蛋白在功能域和三维结构上具有高度的保守性。此外,我们的体外瞬时报告分析在斑马鱼optn基因的上游区域发现了一个功能性启动子,以及一个对其转录调控重要的区域。定点突变显示NF-κB基序负责该区域的激活。总之,通过本研究,我们对斑马鱼的optn进行了表征,我们的结果表明斑马鱼可以被视为研究optn在骨相关疾病中的生物学作用的替代模型。
期刊介绍:
Genome is a monthly journal, established in 1959, that publishes original research articles, reviews, mini-reviews, current opinions, and commentaries. Areas of interest include general genetics and genomics, cytogenetics, molecular and evolutionary genetics, developmental genetics, population genetics, phylogenomics, molecular identification, as well as emerging areas such as ecological, comparative, and functional genomics.