title: Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals.
abstract: 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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schueren
authors.affiliation: Department of Bioinformatics, Institute for Microbiology and Genetics, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lingner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Rosemol
authors.initials: R
authors.lastname: George
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hofhuis
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Dickel
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Thoms
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018388:Codon, Terminator / Q000235:genetics; D003198:Computer Simulation; D017124:Conserved Sequence; D017930:Genes, Reporter; D016678:Genome; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008322:Mammals / Q000378:metabolism*; D008969:Molecular Sequence Data; D020675:Peroxisomes / Q000201:enzymology*; D014176:Protein Biosynthesis; D021382:Protein Sorting Signals; D021381:Protein Transport; D051381:Rats
chemical_list: D018388:Codon, Terminator; D007527:Isoenzymes; D021382:Protein Sorting Signals; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1
keywords: cell biology; gene regulation; genome-wide in silico screen; human; human biology; lactate dehydrogenase; medicine; peroxisomal targeting signal; stop codon suppression; translational readthrough