One SNP in the 3′-UTR of HMGB1 gene affects the binding of target bta-miR-223 and is involved in mastitis in dairy cattle

• Published in: Immunogenetics (New York) Vol. 64; no. 11; pp. 817 - 824
• Main Authors: Li, Liming, Huang, Jinming, Zhang, Xiaojian, Ju, Zhihua, Qi, Chao, Zhang, Yan, Li, Qiuling, Wang, Changfa, Miao, Weiran, Zhong, Jifeng, Hou, Minghai, Hang, Suqin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2012; Springer Nature B.V
• Subjects: 3' Untranslated Regions - genetics; Allergology; Animal sciences; Animals; Base Sequence; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cattle; Cell Biology; Cells, Cultured; Computational Biology; Cytokines; Dairy cattle; Female; Gene expression; Gene Function; Genetic testing; Genotypes; HMGB1 Protein - genetics; Human Genetics; Humans; Immunology; Inflammatory diseases; Luciferases - metabolism; Mastitis, Bovine - genetics; MicroRNAs; MicroRNAs - genetics; Molecular Sequence Data; Nucleic acids; Original Paper; Pathogens; Polymerase chain reaction; Polymorphism; Polymorphism, Single Nucleotide - genetics; Proteins; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Sequence Homology, Nucleic Acid; Zoology; China; Functional SNP; Mastitis; Dairy cattle
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s00251-012-0641-1

High-mobility group box protein 1 ( HMGB1 ) gene has a universal sentinel function for nucleic acid-mediated innate immune responses and acts as a pathogenic mediator in the inflammatory disease. In an effort to identify the functional single-nucleotide polymorphism (SNP) in the 3′-untranslated region (UTR) of the bovine HMGB1 gene that affects the binding to its target microRNA, first, the expression of HMGB1 mRNA in different genotypes and its candidate bta-miR-223 was investigated. Quantitative real-time polymerase chain reaction results showed that the relative expression of HMGB1 mRNA in cows with the genotype GG is significantly higher than those in cows with the genotype AA ( P  < 0.05). The expression of bta-miR-223 was significantly upregulated by 1.95-fold ( P  < 0.05) in the bovine mastitis-infected mammary gland tissues compared with that in the healthy tissues. Subsequently, luciferase assay indicated that the HMGB1 expression was directly targeted by bta-miR-223 in human embryo kidney 293 T (HEK 293T) cells. One novel SNP (g. +2776 A > G) in the HMGB1 3′-UTR, altering the binding of HMGB1 and bta-miR-223 , was found to be associated with somatic count scores in cows. Taken together, the g. +2776 A > G-GG was an advantageous genotype which can be used as a candidate functional marker for mastitis resistance breeding program.