RNF14 is a regulator of mitochondrial and immune function in muscle.
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.
Aaron B
AB
Ingham
Simone A
SA
Osborne
Moira
M
Menzies
Suzie
S
Briscoe
Wei
W
Chen
Kritaya
K
Kongsuwan
Antonio
A
Reverter
Angela
A
Jeanes
Brian P
BP
Dalrymple
Gene
G
Wijffels
Robert
R
Seymour
CSIRO Animal, Food and Health Sciences, 306 Carmody Road, St, Lucia, Queensland, Australia. nick.hudson@csiro.au.
Nicholas J
NJ
Hudson
D020816:Amino Acid Motifs; D000818:Animals; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D059467:Transcriptome / Q000276:immunology
D004268:DNA-Binding Proteins; C486693:Rnf141 protein, mouse; D014157:Transcription Factors