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Phylogenetically Conserved Sequences Around Myelin P0 Stop Codon are Essential for Translational Readthrough to

Yoshihide Yamaguchi1, Hiroko Baba2

  • 1Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. yoshiy@toyaku.ac.jp.

Neurochemical Research
|October 30, 2017
PubMed

Insights

Large myelin protein zero (L-MPZ) is synthesized from frogs to humans due to a conserved sequence around the P0 stop codon. This phylogenetic finding suggests L-MPZ

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Myelin protein zero (P0) is a critical cell adhesion molecule in peripheral myelin, with a highly conserved sequence.
  • Large myelin protein zero (L-MPZ) is a novel translational readthrough product of P0 mRNA, identified in mammals.
  • The synthesis, mechanism, and function of L-MPZ are not fully understood, particularly its phylogenetic distribution.

Purpose of the Study:

  • To investigate the phylogenetic pathways of L-MPZ synthesis.
  • To determine the evolutionary conservation and functional significance of the sequence surrounding the P0 stop codon.

Main Methods:

  • Western blotting was employed to detect L-MPZ production across different species (frogs to humans).
  • A mammalian in vitro transcription/translation system was used for mutation analysis of the P0 stop codon sequence.

Main Results:

  • L-MPZ is widely produced in vertebrates, from frogs to humans, as confirmed by western blotting.
  • The evolutionarily conserved sequence around the P0 stop codon is crucial for L-MPZ synthesis via translational readthrough.
  • This conserved sequence shares similarities with known readthrough motifs in viruses and yeast.

Conclusions:

  • The phylogenetically conserved sequence around the canonical P0 stop codon is essential for L-MPZ synthesis.
  • The emergence of L-MPZ in amphibians may be linked to specific functions within the peripheral nervous system (PNS) myelin.
Keywords:
Large myelin protein zero (L-MPZ)MyelinMyelin protein zero (P0, MPZ)Translational readthrough

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