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Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of terminal oligopyrimidine (TOP) mRNAs on polysomes.

Gismondi, A, Caldarola, S, Lisi, G, Juli, G, Chellini, L, Iadevaia, V, Proud, CG and Loreni, F (2014) Ribosomal stress activates eEF2K-eEF2 pathway causing translation elongation inhibition and recruitment of terminal oligopyrimidine (TOP) mRNAs on polysomes. Nucleic Acids Res, 42 (20). pp. 12668-12680.

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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.

Item Type: Article
Authors :
NameEmailORCID
Gismondi, AUNSPECIFIEDUNSPECIFIED
Caldarola, SUNSPECIFIEDUNSPECIFIED
Lisi, GUNSPECIFIEDUNSPECIFIED
Juli, GUNSPECIFIEDUNSPECIFIED
Chellini, LUNSPECIFIEDUNSPECIFIED
Iadevaia, Vv.iadevaia@surrey.ac.ukUNSPECIFIED
Proud, CGUNSPECIFIEDUNSPECIFIED
Loreni, FUNSPECIFIEDUNSPECIFIED
Date : 10 November 2014
Identification Number : 10.1093/nar/gku996
Uncontrolled Keywords : Cell Line, Tumor, Elongation Factor 2 Kinase, Eukaryotic Initiation Factor-1, Extracellular Signal-Regulated MAP Kinases, Humans, Multiprotein Complexes, Peptide Chain Elongation, Translational, Peptide Elongation Factor 2, Polyribosomes, RNA 5' Terminal Oligopyrimidine Sequence, RNA, Messenger, Ribosomal Proteins, Ribosomes, Stress, Physiological, TOR Serine-Threonine Kinases
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:28
Last Modified : 17 May 2017 14:49
URI: http://epubs.surrey.ac.uk/id/eprint/827931

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