Journal article

Viral regulation of host cell biology by hijacking of the nucleolar DNA-damage response

Stephen M Rawlinson, Tianyue Zhao, Ashley M Rozario, Christina L Rootes, Paul J McMillan, Anthony W Purcell, Amanda Woon, Glenn A Marsh, Kim G Lieu, Lin-Fa Wang, Hans J Netter, Toby DM Bell, Cameron R Stewart, Gregory W Moseley

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

Abstract

Recent studies indicate that nucleoli play critical roles in the DNA-damage response (DDR) via interaction of DDR machinery including NBS1 with nucleolar Treacle protein, a key mediator of ribosomal RNA (rRNA) transcription and processing. Here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar DDR pathway is targeted by infectious pathogens. We find that the matrix proteins of Hendra virus and Nipah virus, highly pathogenic viruses of the Henipavirus genus in the order Mononegavirales, interact with Treacle and inhibit its function, thereby silencing rRNA biogenesis, consistent with mimicki..

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University of Melbourne Researchers

Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council Australia


Awarded by ARC


Awarded by NRF-CRP



Funding Acknowledgements

The authors acknowledge Cassandra David for assistance with tissue culture, and the facilities and technical assistance of Monash Micro Imaging (Monash University) and the Biological Optical Microscopy Platform (University of Melbourne). Mass spectrometry was performed at the Mass Spectrometry and Proteomics facility at the Bio21 Institute (University of Melbourne) and at the Monash Biomedical Proteomics Facility (Monash University). The authors thank Angus I. Lamond (University of Dundee) for helpful discussions and acknowledge his contributions to securing funding (Australian Research Council (ARC) grant DP150102569). This work was supported by: National Health and Medical Research Council Australia grants 1125704 & 1079211 to G.W.M., and 1044228 to H.J.N.; ARC grant DP150102569 to G.W.M., L.F.W. and Angus I. Lamond (University of Dundee); DP170104477 to T.D.M.B.; Grimwade Fellowship, Meigunyah Fund to G.W.M.; NRF-CRP grant NRF2012NRF-CRP001-056 to L.F.W.