Phosphorothioate Modification of mRNA Accelerates the Rate of Translation Initiation to Provide More Efficient Protein Synthesis

Daisuke Kawaguchi, Ayumi Kodama, Naoko Abe, Kei Takebuchi, Fumitaka Hashiya, Fumiaki Tomoike, Kosuke Nakamoto, Yasuaki Kimura, Yoshihiro Shimizu, Hiroshi Abe

Research output: Contribution to journalArticle

Abstract

Messenger RNAs (mRNAs) with phosphorothioate modification (PS-mRNA) to the phosphate site of A, G, C, and U with all 16 possible combinations were prepared, and the translation reaction was evaluated using an E. coli cell-free translation system. Protein synthesis from PS-mRNA increased in 12 of 15 patterns when compared with that of unmodified mRNA. The protein yield increased 22-fold when the phosphorothioate modification at A/C sites was introduced into the region from the 5′-end to the initiation codon. Single-turnover analysis of PS-mRNA translation showed that phosphorothioate modification increases the number of translating ribosomes, thus suggesting that the rate of translation initiation (rate of ribosome complex formation) is positively affected by the modification. The method provides a new strategy for improving translation by using non-natural mRNA.

Original languageEnglish
Pages (from-to)17403-17407
Number of pages5
JournalAngewandte Chemie - International Edition
Volume59
Issue number40
DOIs
Publication statusPublished - Sep 28 2020

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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