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https://hdl.handle.net/2440/105368
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Type: | Journal article |
Title: | Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of Terminal Oligopyrimidine (TOP) mRNAs on polysomes |
Author: | Gismondi, A. Caldarola, S. Lisi, G. Juli, G. Chellini, L. Iadevaia, V. Proud, C. Loreni, F. |
Citation: | Nucleic Acids Research, 2014; 42(20):12668-12680 |
Publisher: | Oxford University Press |
Issue Date: | 2014 |
ISSN: | 0305-1048 1362-4962 |
Statement of Responsibility: | Angelo Gismondi, Sara Caldarola, Gaia Lisi, Giada Juli, Lidia Chellini, Valentina Iadevaia, Christopher G. Proud and Fabrizio Loreni |
Abstract: | The synthesis of adequate amounts of ribosomes is an essential task for the cell. It is therefore not surprising that regulatory circuits exist to organize the synthesis of ribosomal components. It has been shown that defect in ribosome biogenesis (ribosomal stress) induces apoptosis or cell cycle arrest through activation of the tumor suppressor p53. This mechanism is thought to be implicated in the pathophysiology of a group of genetic diseases such as Diamond Blackfan Anemia which are called ribosomopathies. We have identified an additional response to ribosomal stress that includes the activation of eukaryotic translation elongation factor 2 kinase with a consequent inhibition of translation elongation. This leads to a translational reprogramming in the cell that involves the structurally defined group of messengers called terminal oligopyrimidine (TOP) mRNAs which encode ribosomal proteins and translation factors. In fact, while general protein synthesis is decreased by the impairment of elongation, TOP mRNAs are recruited on polysomes causing a relative increase in the synthesis of TOP mRNA-encoded proteins compared to other proteins. Therefore, in response to ribosomal stress, there is a change in the translation pattern of the cell which may help restore a sufficient level of ribosomes. |
Keywords: | Ribosomal stress; peptide chain elongation |
Rights: | © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1093/nar/gku996 |
Published version: | http://dx.doi.org/10.1093/nar/gku996 |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
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hdl_105368.pdf | Published version | 2.88 MB | Adobe PDF | View/Open |
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