The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Clarke, Kim; Ricciardi, Sara; Pearson, Tim; Bharudin, Izwan; Davidsen, Peter K.; Bonomo, Michela; Brina, Daniela; Scagliola, Alessandra; Simpson, Deborah M.; Beynon, Robert J.; Khanim, Farhat L.; Ankers, John; Sarzynski, Mark A.; Ghosh, Sujoy; Pisconti, Addolorata; Rozman, Jan; Angelis, Martin Hrabě de; Bunce, Christopher M.; Stewart, Claire E.; Egginton, Stuart; Caddick, Mark X.; Jackson, Malcolm J.; Bouchard, Claude; Biffo, Stefano; Falciani, Francesco

doi:10.1016/j.celrep.2017.10.040

Cited by 23 publications

(24 citation statements)

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“…Decades of research have demonstrated that skeletal muscle is one of the most dynamic tissues in the body. Muscle has an inherent ability to fine tune its response to environmental and physiological changes, including but not limited to exercise, diet, disuse, and disease [10][11][12][13]. Many adaptations of skeletal muscle are through transcriptional programs that modulate patterns of gene expression.…”

Section: Extensive Rna Processing In Muscle Biologymentioning

confidence: 99%

RNA processing in skeletal muscle biology and disease

2019

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RNA processing encompasses the capping, cleavage, polyadenylation and alternative splicing of pre-mRNA. Proper muscle development relies on precise RNA processing, driven by the coordination between RNA-binding proteins. Recently, skeletal muscle biology has been intensely investigated in terms of RNA processing. High throughput studies paired with deletion of RNA-binding proteins have provided a high-level understanding of the molecular mechanisms controlling the regulation of RNA-processing in skeletal muscle. Furthermore, misregulation of RNA processing is implicated in muscle diseases. In this review, we comprehensively summarize recent studies in skeletal muscle that demonstrated: (i) the importance of RNA processing, (ii) the RNA-binding proteins that are involved, and (iii) diseases associated with defects in RNA processing. ARTICLE HISTORY

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Section: Extensive Rna Processing In Muscle Biologymentioning

confidence: 99%

RNA processing in skeletal muscle biology and disease

2019

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“…EV pellets were digested and acidified as described previously (Clarke et al, 2017), and the completeness of digestion and bta-mir-181b target genes encoding BOLA class 1 (bovine MHC class 1), ICAM-1, and MMP-9 were amplified from TBL20 genomic DNA, using PfuUltra II Fusion HS DNA Polymerase (Agilent). EV pellets were digested and acidified as described previously (Clarke et al, 2017), and the completeness of digestion and bta-mir-181b target genes encoding BOLA class 1 (bovine MHC class 1), ICAM-1, and MMP-9 were amplified from TBL20 genomic DNA, using PfuUltra II Fusion HS DNA Polymerase (Agilent).…”

Section: Proteomic Sample Preparation and Lc-ms Analysismentioning

confidence: 99%

“…Six biological replicates were used for proteomic analysis of BL20-EV and TBL20-EV. EV pellets were digested and acidified as described previously (Clarke et al, 2017), and the completeness of digestion and bta-mir-181b target genes encoding BOLA class 1 (bovine MHC class 1), ICAM-1, and MMP-9 were amplified from TBL20 genomic DNA, using PfuUltra II Fusion HS DNA Polymerase (Agilent). These genes were selected based upon their potential importance in the pathogenesis of Theileria infection and relevance to disease progression.…”

Section: Proteomic Sample Preparation and Lc-ms Analysismentioning

confidence: 99%

“…LC-MS analysis was conducted on a QExactive HF quadrupole-Orbitrap mass spectrometer coupled to a Dionex Ultimate 3000 RSLC nano-liquid chromatograph (Hemel Hempstead, United Kingdom) described in(Clarke et al, 2017). LC-MS analysis was conducted on a QExactive HF quadrupole-Orbitrap mass spectrometer coupled to a Dionex Ultimate 3000 RSLC nano-liquid chromatograph (Hemel Hempstead, United Kingdom) described in(Clarke et al, 2017).…”

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confidence: 99%

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Characterisation of infection associated microRNA and protein cargo in extracellular vesicles ofTheileria annulatainfected leukocytes

Gillan

Simpson

Kinnaird

et al. 2018

Cellular Microbiology

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The protozoan parasites Theileria annulata and Theileria parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation‐like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a subset of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here, we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T. annulata (TBL20) by comparative mass spectrometry and microRNA (miRNA) profiling (data available via ProteomeXchange, identifier PXD010713 and NCBI GEO, accession number GSE118456, respectively). Ingenuity pathway analysis that many infection‐associated proteins essential to migration and extracellular matrix digestion were upregulated in EV from TBL20 cells compared with BL20 controls. An altered repertoire of host miRNA, many with known roles in tumour and/or infection biology, was also observed. Focusing on the tumour suppressor miRNA, bta‐miR‐181a and bta‐miR‐181b, we identified putative messenger RNA targets and confirmed the interaction of bta‐miR181a with ICAM‐1. We propose that EV and their miRNA cargo play an important role in the manipulation of the host cell phenotype and the pathobiology of Theileria infection.

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“…Similar defects in translation are also observed in vivo, where livers of eIF6+/-mice are smaller, and exhibit an accumulation of inactive/empty (mRNA-free) 80S ribosomes compared to WT [17][18][19] . The lack of insulin-dependent stimulation of protein synthesis in the eIF6+/-mice has been associated with a reprogramming of fatty acid synthesis and glycolytic pathways with implications for muscle, liver and fat metabolism 19,21 .…”

Section: Introductionmentioning

confidence: 99%

Regulation of eIF6 through multisite and sequential phosphorylation by GSK3β

Jungers

Elliff

Masson-Meyers

et al. 2018

Preprint

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Eukaryotic translation initiation factor 6 is essential for the synthesis of 60S ribosomal subunits and for regulating the association of 60S and 40S ribosomal subunits. A mechanistic understanding of how eIF6 modulates protein synthesis in response to stress, specifically starvation-induced stress, is lacking. Our studies have uncovered a novel mode of eIF6 regulation by Glycogen Synthase Kinase-3 that is predominantly active in response to serum starvation. Human eIF6 is phosphorylated by GSK3 at a multisite motif in the C-terminal tail.Robust and sequential phosphorylation by GSK3 requires phosphorylation at a priming site. In response to serum starvation, eIF6 accumulates in the cytoplasm and this altered subcellular localization is dependent on GSK3 activity. Cells expressing the phosphodead mutant exhibit increased levels of free 60S subunits and display a further inhibition translation in response to serum starvation, which deregulates the cellular response to starvation. These results suggest that eIF6 regulation by GSK3 contributes to the attenuation of global protein synthesis that is critical for adaptation to starvation-induced stress.

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The Role of Eif6 in Skeletal Muscle Homeostasis Revealed by Endurance Training Co-expression Networks

Cited by 23 publications

References 50 publications

RNA processing in skeletal muscle biology and disease

RNA processing in skeletal muscle biology and disease

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles ofTheileria annulatainfected leukocytes

Regulation of eIF6 through multisite and sequential phosphorylation by GSK3β

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