title: A MicroRNA-Mediated Positive Feedback Regulatory Loop of the NF-κB Pathway in Litopenaeus vannamei.
abstract: In the evolutionarily conserved canonical NF-κB pathway, degradation of the NF-κB inhibitor IκB in the cytoplasmic NF-κB/IκB complex allows the liberated NF-κB to translocate into the nucleus to activate various target genes. The regulatory mechanism governing this process needs further investigation. In this study, a novel microRNA, temporarily named miR-1959, was first identified from an invertebrate Litopenaeus vannamei miR-1959 targets the 3'-untranslated region of the IκB homolog Cactus gene and reduces the protein level of Cactus in vivo, whereas the NF-κB homolog Dorsal directly binds the miR-1959 promoter to activate its transcription. Therefore, miR-1959 mediates a positive feedback regulatory loop, in that Dorsal activates miR-1959 expression, and in turn, miR-1959 inhibits the expression of Cactus, further leading to enhanced activation of Dorsal. Moreover, miR-1959 regulates the expression of many antimicrobial peptides in vivo and is involved in antibacterial immunity. To our knowledge, it is the first discovery of a microRNA-mediated feedback loop that directly regulates the NF-κB/IκB complex. This positive feedback loop could collaborate with the known NF-κB/IκB negative loop to generate a dynamic balance to regulate the activity of NF-κB, thus constituting an effective regulatory mechanism at the critical node of the NF-κB pathway.
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; South China Sea Resource Exploitation and Protection Collaborative Innovation Center, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China; and.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Zuo
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;
authors.forename: Jia
authors.initials: J
authors.lastname: Yuan
authors.affiliation: South China Sea Resource Exploitation and Protection Collaborative Innovation Center, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China; and.
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Fisheries Research Institute of Zhanjiang, Zhanjiang 524039, China.
authors.forename: Sedong
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Su
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;
authors.forename: Erman
authors.initials: E
authors.lastname: Wei
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China; and.
authors.forename: Chaozheng
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China;
authors.forename: Shaoping
authors.initials: S
authors.lastname: Weng
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China; and xuxpeng@mail.sysu.edu.cn lsshjg@mail.sysu.edu.cn.
authors.forename: Xiaopeng
authors.identifier: 0000-0002-8248-5042
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Ministry of Education Key Laboratory of Aquatic Product Safety, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Institute of Aquatic Economic Animals, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China; South China Sea Resource Exploitation and Protection Collaborative Innovation Center, Guangzhou 510275, China; Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510275, China; and xuxpeng@mail.sysu.edu.cn lsshjg@mail.sysu.edu.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics; D005075:Biological Evolution; D002467:Cell Nucleus / Q000378:metabolism*; D003001:Cloning, Molecular; D025461:Feedback, Physiological; D051550:I-kappa B Kinase / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D033561:Penaeidae / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D023181:Antimicrobial Cationic Peptides; D035683:MicroRNAs; D016328:NF-kappa B; D051550:I-kappa B Kinase