TY  - JOUR
A1  - Stiebler, Alina C.
A1  - Freitag, Johannes
A1  - Schink, Kay O.
A1  - Stehlik, Thorsten
A1  - Tillmann, Britta A. M.
A1  - Ast, Julia
A1  - Bölker, Michael
T1  - Ribosomal readthrough at a short UGA stop codon context triggers dual localization of metabolic enzymes in fungi and animals
T2  - PLoS Genetics
N2  - 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.
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35304
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-353049
SN  - 1553-7404
SN  - 1553-7390
N1  - 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.
VL  - 10
IS  - (10):e1004685
PB  - PLoS
CY  - Lawrence, Kan.
ER  -