Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila

Cell Rep. 2018 Aug 14;24(7):1704-1712. doi: 10.1016/j.celrep.2018.07.039.

Abstract

Tissue-specific mRNA stability is important for cell fate and physiology, but the mechanisms involved are not fully understood. We found that zygotic mRNA stability in Drosophila correlates with codon content: optimal codons are enriched in stable transcripts associated with metabolic functions like translation, while non-optimal codons are enriched in unstable transcripts, including those associated with neural development. Bioinformatic analyses and reporter assays revealed that similar codons stabilize or destabilize mRNAs in the nervous system and other tissues, but the link between codon content and stability is attenuated in the nervous system. We confirmed that optimal codons are decoded by abundant tRNAs while non-optimal codons are decoded by less abundant tRNAs in embryos and in the nervous system. We conclude that codon optimality is a general determinant of zygotic mRNA stability, and attenuation of codon optimality allows trans-acting factors to exert greater influence over mRNA decay in the nervous system.

Keywords: Drosophila; codon optimality; development; mRNA stability; nervous system; tRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Codon / chemistry*
  • Codon / metabolism
  • Computational Biology / methods
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental*
  • Half-Life
  • Humans
  • Neurogenesis / genetics
  • Protein Biosynthesis*
  • RNA Stability
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Transfer / genetics*
  • RNA, Transfer / metabolism
  • Zygote / growth & development
  • Zygote / metabolism

Substances

  • Codon
  • RNA, Messenger
  • RNA, Transfer