Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals

Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identif...

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Autores principales: Schueren, Fabian, Lingner, Thomas, George, Rosemol, Hofhuis, Julia, Dickel, Corinna, Gärtner, Jutta, Thoms, Sven
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2014
Materias:
Cell Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359377/
https://www.ncbi.nlm.nih.gov/pubmed/25247702
http://dx.doi.org/10.7554/eLife.03640
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author Schueren, Fabian
Lingner, Thomas
George, Rosemol
Hofhuis, Julia
Dickel, Corinna
Gärtner, Jutta
Thoms, Sven
author_facet Schueren, Fabian
Lingner, Thomas
George, Rosemol
Hofhuis, Julia
Dickel, Corinna
Gärtner, Jutta
Thoms, Sven
author_sort Schueren, Fabian
collection PubMed
description Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB is targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit, into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes. DOI: http://dx.doi.org/10.7554/eLife.03640.001
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spelling pubmed-43593772015-03-16 Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals Schueren, Fabian Lingner, Thomas George, Rosemol Hofhuis, Julia Dickel, Corinna Gärtner, Jutta Thoms, Sven eLife Cell Biology Translational readthrough gives rise to low abundance proteins with C-terminal extensions beyond the stop codon. To identify functional translational readthrough, we estimated the readthrough propensity (RTP) of all stop codon contexts of the human genome by a new regression model in silico, identified a nucleotide consensus motif for high RTP by using this model, and analyzed all readthrough extensions in silico with a new predictor for peroxisomal targeting signal type 1 (PTS1). Lactate dehydrogenase B (LDHB) showed the highest combined RTP and PTS1 probability. Experimentally we show that at least 1.6% of the total cellular LDHB is targeted to the peroxisome by a conserved hidden PTS1. The readthrough-extended lactate dehydrogenase subunit LDHBx can also co-import LDHA, the other LDH subunit, into peroxisomes. Peroxisomal LDH is conserved in mammals and likely contributes to redox equivalent regeneration in peroxisomes. DOI: http://dx.doi.org/10.7554/eLife.03640.001 eLife Sciences Publications, Ltd 2014-09-23 /pmc/articles/PMC4359377/ /pubmed/25247702 http://dx.doi.org/10.7554/eLife.03640 Text en © 2014, Schueren et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Schueren, Fabian
Lingner, Thomas
George, Rosemol
Hofhuis, Julia
Dickel, Corinna
Gärtner, Jutta
Thoms, Sven
Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title_full Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title_fullStr Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title_full_unstemmed Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title_short Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
title_sort peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359377/
https://www.ncbi.nlm.nih.gov/pubmed/25247702
http://dx.doi.org/10.7554/eLife.03640
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