RTN3 is a novel cold-induced protein and mediates neuroprotective effects of RBM3

Bastide, A. et al. (2017) RTN3 is a novel cold-induced protein and mediates neuroprotective effects of RBM3. Current Biology, 27(5), pp. 638-650. (doi: 10.1016/j.cub.2017.01.047) (PMID:28238655) (PMCID:PMC5344685)

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Cooling and hypothermia are profoundly neuroprotective, mediated, at least in part, by the cold shock protein, RBM3. However, the neuroprotective effector proteins induced by RBM3 and the mechanisms by which mRNAs encoding cold shock proteins escape cooling-induced translational repression are unknown. Here, we show that cooling induces reprogramming of the translatome, including the upregulation of a new cold shock protein, RTN3, a reticulon protein implicated in synapse formation. We report that this has two mechanistic components. Thus, RTN3 both evades cooling-induced translational elongation repression and is also bound by RBM3, which drives the increased expression of RTN3. In mice, knockdown of RTN3 expression eliminated cooling-induced neuroprotection. However, lentivirally mediated RTN3 overexpression prevented synaptic loss and cognitive deficits in a mouse model of neurodegeneration, downstream and independently of RBM3. We conclude that RTN3 expression is a mediator of RBM3-induced neuroprotection, controlled by novel mechanisms of escape from translational inhibition on cooling.

Item Type:Articles
Additional Information:The work was funded by the BBSRC (BB/I019790/1; A.B., A.R., J.R., J.R.P.K., and R.V.S.), MRC (D.P., programme grant, 5TR50 to G.R.M.; S.G., programme funding, 5TR00 to A.E.W.), and Wellcome Trust (2010847/Z/16/Z; S.G., collaborative award to A.E.W., G.R.M., C.M.S., and T.v.d.H.).
Glasgow Author(s) Enlighten ID:Bushell, Professor Martin
Authors: Bastide, A., Peretti, D., Knight, J. R.P., Grosso, S., Spriggs, R. V., Pichon, X., Sbarrato, T., Roobol, A., Roobol, J., Vito, D., Bushell, M., von der Haar, T., Smales, C. M., Mallucci, G. R., and Willis, A. E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Current Biology
Publisher:Elsevier (Cell Press)
ISSN (Online):1879-0445
Published Online:23 February 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Current Biology 27(5): 638-650
Publisher Policy:Reproduced under a Creative Commons License

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