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 getting 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.
Article and author information
Author details
Reviewing Editor
- Nahum Sonenberg, McGill University, Canada
Version history
- Received: June 9, 2014
- Accepted: September 22, 2014
- Accepted Manuscript published: September 23, 2014 (version 1)
- Version of Record published: October 16, 2014 (version 2)
Copyright
© 2014, Schueren et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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