MULAN related gene (MRG): a potential novel ubiquitin ligase activator of NF-kB involved in immune response in Atlantic salmon (Salmo salar)

Abstract

Nuclear factor-kB (NF-kB) is a transcription factor that plays a central role in the regulation of a variety of genes including many involved in bacterial and viral infections. NF-kB is normally sequestered by inhibitory proteins (IkBs) in the cytoplasm of non-stimulated cells. The degradation of IkBs by the ubiquitin proteasome pathway releases NF-kB allowing its translocation to the nucleus where it regulates gene transcription. The Mitochondrial Ubiquitin Ligase Activator of NF-kB, (MULAN), is an E3 ubiquitin ligase involved in controlling activation of NF-kB, and regulating mitochondrial dynamics and apoptosis. We report the characterisation of a novel piscine-specific MULAN related gene (MRG) sequence, its mRNA tissue distribution and expression following in vivo and in vitro challenges. MRG cDNA was identified in Atlantic salmon and its sequence encodes a predicted protein of 274 amino acids. The mRNA of MRG was expressed in multiple tissues, with the highest abundance head kidney. An Aeromonas salmonicida bacterial challenge increased expression of this gene in head kidney, liver and gill tissue at 6 h and 24 h. In vitro stimulation of a salmonid cell line indicated MRG was increased in expression following stimulation with LPS, PolyI:C and recombinant trout IL-1β for 4 h and 24 h. These results suggest an active role of MRG in the activation of the NF-kB pathway during early immune responses.