Ribosomal readthrough at a short UGA stop codon context triggers dual localization of metabolic enzymes in fungi and animals

Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing eviden
Translation of mRNA into a polypeptide chain is a highly accurate process. Many prokaryotic and eukaryotic viruses, however, use leaky termination of translation to optimize their coding capacity. Although growing evidence indicates the occurrence of ribosomal readthrough also in higher organisms, a biological function for the resulting extended proteins has been elucidated only in very few cases. Here, we report that in human cells programmed stop codon readthrough is used to generate peroxisomal isoforms of cytosolic enzymes. We could show for NAD-dependent lactate dehydrogenase B (LDHB) and NAD-dependent malate dehydrogenase 1 (MDH1) that translational readthrough results in C-terminally extended protein variants containing a peroxisomal targeting signal 1 (PTS1). Efficient readthrough occurs at a short sequence motif consisting of a UGA termination codon followed by the dinucleotide CU. Leaky termination at this stop codon context was observed in fungi and mammals. Comparative genome analysis allowed us to identify further readthrough-derived peroxisomal isoforms of metabolic enzymes in diverse model organisms. Overall, our study highlights that a defined stop codon context can trigger efficient ribosomal readthrough to generate dually targeted protein isoforms. We speculate that beyond peroxisomal targeting stop codon readthrough may have also other important biological functions, which remain to be elucidated.
show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

    Share in Twitter Search Google Scholar
Metadaten
Author:Alina C. Stiebler, Johannes Freitag, Kay O. Schink, Thorsten Stehlik, Britta A. M. Tillmann, Julia Ast, Michael Bölker
URN:urn:nbn:de:hebis:30:3-353049
DOI:http://dx.doi.org/10.1371/journal.pgen.1004685
ISSN:1553-7404
ISSN:1553-7390
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25340584
Parent Title (English):PLoS Genetics
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2014/10/23
Date of first Publication:2014/10/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2014/11/08
Volume:10
Issue:(10):e1004685
Pagenumber:9
Note:
Copyright: © 2014 Stiebler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:366639641
Institutes:Biowissenschaften
Senckenbergische Naturforschende Gesellschaft
Dewey Decimal Classification:570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 4.0

$Rev: 11761 $