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Specialized Yeast Ribosomes: A Customized Tool for Selective mRNA Translation

Preiss, Thomas, Bauer, Johann W., Brandl, Clemens, Haubenreisser, Olaf, Wimmer, Bjoern, Weber, Manuela, Karl, Thomas, Klausegger, Alfred, Breitenbach, Michael, Hintner, Helmut, and others. (2013) Specialized Yeast Ribosomes: A Customized Tool for Selective mRNA Translation. PLoS ONE, 8 (7). e67609. ISSN 1932-6203. (doi:10.1371/journal.pone.0067609) (KAR id:35626)

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http://dx.doi.org/10.1371/journal.pone.0067609

Abstract

Evidence is now accumulating that sub-populations of ribosomes - so-called specialized ribosomes - can favour the translation of subsets of mRNAs. Here we use a large collection of diploid yeast strains, each deficient in one or other copy of the set of ribosomal protein (RP) genes, to generate eukaryotic cells carrying distinct populations of altered ‘specialized’ ribosomes. We show by comparative protein synthesis assays that different heterologous mRNA reporters based on luciferase are preferentially translated by distinct populations of specialized ribosomes. These mRNAs include reporters carrying premature termination codons (PTC) thus allowing us to identify specialized ribosomes that alter the efficiency of translation termination leading to enhanced synthesis of the wild-type protein. This finding suggests that these strains can be used to identify novel therapeutic targets in the ribosome. To explore this further we examined the translation of the mRNA encoding the extracellular matrix protein laminin ?3 (LAMB3) since a LAMB3-PTC mutant is implicated in the blistering skin disease Epidermolysis bullosa (EB). This screen identified specialized ribosomes with reduced levels of RP L35B as showing enhanced synthesis of full-length LAMB3 in cells expressing the LAMB3-PTC mutant. Importantly, the RP L35B sub-population of specialized ribosomes leave both translation of a reporter luciferase carrying a different PTC and bulk mRNA translation largely unaltered.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0067609
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Tobias von der Haar
Date Deposited: 24 Oct 2013 16:16 UTC
Last Modified: 06 May 2020 03:08 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/35626 (The current URI for this page, for reference purposes)
von der Haar, Tobias: https://orcid.org/0000-0002-6031-9254
Tuite, Mick F.: https://orcid.org/0000-0002-5214-540X
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