A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy

Javier Torres-Torronteras, Agustí Rodriguez-Palmero, Tomàs Pinós, Anna Accarino, Antoni L. Andreu, Guillem Pintos-Morell, Ramon Martíí

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Abstract

The cellular quality control systems enable surveillance and selective degradation of nonsense, nonstop, and no-go mRNAs. In the case of nonstop mRNA, different mechanisms of nonstop-mediated decay (NSD) have been described for bacteria, yeast and mammals, but the molecular consequences of nonstop mutations have been examined in only few cases of human disease. We describe a novel homozygous nonstop mRNA mutation (c.1416delC) in the TYMP gene encoding thymidine phosphorylase, in a patient with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). In contrast to previous reports showing selective decay of pathogenic nonstop mRNAs, quantitative real-time PCR and 3'-RACE-RFLP analysis revealed unreduced nonstop mRNA levels in our patient and 2 heterozygous carriers of the mutation. The absence of thymidine phosphorylase protein in the homozygous patient, together with the partial decrease in levels of this protein in 2 carriers suggest that the main control system in this case resides at the translational or post-translational levels rather than through NSD. This is the first report showing an absence of NSD in a human disease, revealing that this surveillance mechanism has exceptions in vivo. © 2011 Wiley-Liss, Inc.
Original languageEnglish
JournalHuman Mutation
Volume32
Issue number4
DOIs
Publication statusPublished - 1 Apr 2011

Keywords

  • MNGIE
  • Neuropathy
  • Nonstop mediated decay
  • Nonstop mutation
  • NSD
  • TYMP

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    Torres-Torronteras, J., Rodriguez-Palmero, A., Pinós, T., Accarino, A., Andreu, A. L., Pintos-Morell, G., & Martíí, R. (2011). A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy. Human Mutation, 32(4). https://doi.org/10.1002/humu.21447