Skip to main content

RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3

Bastide, Amandine, Peretti, Diego, Knight, John R.P., Grosso, Stefano, Spriggs, Ruth V., Pichon, Xavier, Sbarrato, Thomas, Roobol, Anne, Roobol, Jo, Vito, Davide, and others. (2017) RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3. Current Biology, 27 (5). pp. 638-650. ISSN 0960-9822. (doi:10.1016/j.cub.2017.01.047)

Abstract

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: Article
DOI/Identification number: 10.1016/j.cub.2017.01.047
Uncontrolled keywords: cold shock; protein synthesis; mRNA translation; RTN3; neuroprotection; RBM3
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Mark Smales
Date Deposited: 07 Mar 2017 14:06 UTC
Last Modified: 01 Aug 2019 10:41 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/60753 (The current URI for this page, for reference purposes)
von der Haar, Tobias: https://orcid.org/0000-0002-6031-9254
Smales, Christopher Mark: https://orcid.org/0000-0002-2762-4724
  • Depositors only (login required):

Downloads

Downloads per month over past year