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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.

SUBMITTER: Schueren F

PROVIDER: S-EPMC4359377 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals.

Schueren Fabian F Lingner Thomas T George Rosemol R Hofhuis Julia J Dickel Corinna C Gärtner Jutta J Thoms Sven S

eLife 20140923

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 dehydr ...[more]

PMID: 25247702

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