Affiliation:
1. State Key Laboratory for Biocontrol, Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China
2. Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang Bay, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai 519082, China
3. Guangdong Province Key Laboratory for Aquatic Economic Animals, School of life Sciences, Sun Yat-sen University, Guangzhou 510275, China
Abstract
Mammalia cysteamine (2-aminoethanethiol) dioxygenase (ADO) controls the stability of the regulator of G protein signaling 4 (RGS4) through the Cys branch of the Arg/N-degron pathway, thereby affecting the response of the body to hypoxia. However, the oxygen-sensing function of ADO remains unknown in teleost fish. Mandarin fish (Siniperca chuatsi) is one of the most important freshwater economic fishes in China. As the scale of the rearing density continues to increase, hypoxia has become an important factor threatening the growth of mandarin fish. Herein, the molecular characterization, the oxygen-sensing enzyme function, and the role in virus infection of ADO from mandarin fish (scADO) were explored. Bioinformation analysis results showed that scADO had all the molecular foundations for achieving thiol dioxygenase function: three histidine residues coordinated with Fe(II), PCO/ADO domain, and a “jelly roll” β-barrel structure. The expression pattern analysis showed that scAdo was highly expressed in the immune-related tissues, liver, and kidneys and responded to hypoxia on the expression level. Protein degradation experiment results revealed that scADO could lead to the degradation of RGS4 protein through the Cys branch of the Arg/N-degron pathway. Furthermore, the expression levels of scADO responded to fish virus infection. scADO could significantly promote the replication of Siniperca chuatsi rhabdovirus, and this was associated with its thiol dioxygenase activity. These findings not only demonstrate scADO as an oxygen-sensing protein in teleost fish, but are also of considerable importance for clarifying the contribution of the mechanism of hypoxia to the outbreaks of fish viruses.
Funder
National Key Research and Development Program of China
Guangdong Key Research and Development Program
China Agriculture Research System of MOF and MARA
Guangdong Basic and Applied Basic Research Foundation
Key-Area Research and Development Program of Guangdong Province
Guangdong Laboratory for Lingnan Modern Agriculture
Guangdong Provincial Special Fund for Modern Agriculture Industry Technology Innovation Teams
Zhuhai basic and applied basic research project
Basic and Applied Basic Research Project of Guangzhou Science and Technology Plan Project
Subject
Virology,Infectious Diseases