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) (KAR id:60753)
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Language: English 
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| Official URL: https://doi.org/10.1016/j.cub.2017.01.047 |
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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 |
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| 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: | Divisions > Division of Natural Sciences > Biosciences |
| Depositing User: | Mark Smales |
| Date Deposited: | 07 Mar 2017 14:06 UTC |
| Last Modified: | 05 Nov 2024 10:54 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/60753 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Roobol, Anne.
| Creator's ORCID: | |
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| CReDIT Contributor Roles: |
von der Haar, Tobias.
| Creator's ORCID: |
 https://orcid.org/0000-0002-6031-9254
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| CReDIT Contributor Roles: |
Smales, Christopher Mark.
| Creator's ORCID: |
https://orcid.org/0000-0002-2762-4724
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| CReDIT Contributor Roles: |
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