RNF14 is a regulator of mitochondrial and immune function in muscle

BMC Systems Biology

Nicholas J Hudson²  Robert Seymour²  Gene Wijffels²  Brian P Dalrymple²  Angela Jeanes¹  Antonio Reverter²  Kritaya Kongsuwan²  Wei Chen²  Suzie Briscoe²  Moira Menzies²  Simone A Osborne²  Aaron B Ingham² 

[1] School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, Australia;CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St. Lucia, Queensland, Australia

关键词: Networks;    Muscle;    RNF14;    Inflammation;    Mitochondria;   

Others  :  1141458
DOI  :  10.1186/1752-0509-8-10

 received in 2013-04-30, accepted in 2014-01-21,  发布年份 2014

【 摘 要 】

Background

Muscle development and remodelling, mitochondrial physiology and inflammation are thought to be inter-related and to have implications for metabolism in both health and disease. However, our understanding of their molecular control is incomplete.

Results

In this study we have confirmed that the ring finger 14 protein (RNF14), a poorly understood transcriptional regulator, influences the expression of both mitochondrial and immune-related genes. The prediction was based on a combination of network connectivity and differential connectivity in cattle (a non-model organism) and mice data sets, with a focus on skeletal muscle. They assigned similar probability to mammalian RNF14 playing a regulatory role in mitochondrial and immune gene expression. To try and resolve this apparent ambiguity we performed a genome-wide microarray expression analysis on mouse C2C12 myoblasts transiently transfected with two Rnf14 transcript variants that encode 2 naturally occurring but different RNF14 protein isoforms. The effect of both constructs was significantly different to the control samples (untransfected cells and cells transfected with an empty vector). Cluster analyses revealed that transfection with the two Rnf14 constructs yielded discrete expression signatures from each other, but in both cases a substantial set of genes annotated as encoding proteins related to immune function were perturbed. These included cytokines and interferon regulatory factors. Additionally, transfection of the longer transcript variant 1 coordinately increased the expression of 12 (of the total 13) mitochondrial proteins encoded by the mitochondrial genome, 3 of which were significant in isolated pair-wise comparisons (Mt-coxII, Mt-nd2 and mt-nd4l). This apparent additional mitochondrial function may be attributable to the RWD protein domain that is present only in the longer RNF14 isoform.

Conclusions

RNF14 influences the expression of both mitochondrial and immune related genes in a skeletal muscle context, and has likely implications for the inter-relationship between bioenergetic status and inflammation.

【 授权许可】

   
2014 Ingham et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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