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 journalArticlepeer-review

    26 Citations (Scopus)

    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 - Sept 28 2020

    All Science Journal Classification (ASJC) codes

    • Catalysis
    • General Chemistry

    Fingerprint

    Dive into the research topics of 'Phosphorothioate Modification of mRNA Accelerates the Rate of Translation Initiation to Provide More Efficient Protein Synthesis'. Together they form a unique fingerprint.

    Cite this