Nucleic Acids Research2022，Vol.50Issue(16) ：21.DOI:10.1093/nar/gkac722

2 '-O-Methylation of the second transcribed nucleotide within the mRNA 5 ' cap impacts the protein production level in a cell-specific manner and contributes to RNA immune evasion

Drazkowska, Karolina Tomecki, Rafal Warminski, Marcin Baran, Natalia Cysewski, Dominik Depaix, Anais Kasprzyk, Renata Kowalska, Joanna Jemielity, Jacek Sikorski, Pawel J.
Nucleic Acids Research2022，Vol.50Issue(16) ：21.DOI:10.1093/nar/gkac722
✕
  • NSTL
  • Oxford Univ Press

2 '-O-Methylation of the second transcribed nucleotide within the mRNA 5 ' cap impacts the protein production level in a cell-specific manner and contributes to RNA immune evasion

Drazkowska, Karolina 1Tomecki, Rafal 1Warminski, Marcin 1Baran, Natalia 1Cysewski, Dominik 1Depaix, Anais 1Kasprzyk, Renata 1Kowalska, Joanna 1Jemielity, Jacek 1Sikorski, Pawel J.1
扫码查看

作者信息

  • 1. Univ Warsaw
  • 折叠

Abstract

In mammals, m(7)G-adjacent nucleotides undergo extensive modifications. Ribose of the first or first and second transcribed nucleotides can be subjected to 2 '-O-methylation to form cap1 or cap2, respectively. When the first transcribed nucleotide is 2 '-O-methylated adenosine, it can be additionally modified to N6,2 '-O-dimethyladenosine (m(6)A(m)). Recently, the crucial role of cap1 in distinguishing between 'self' and 'non-self' in mammalian cells during viral infection was revealed. Here, we attempted to understand the impact of cap methylations on RNA-related processes. Therefore, we synthesized tetranucleotide cap analogues and used them for RNA capping during in vitro transcription. Using this tool, we found that 2 '-O-methylation of the second transcribed nucleotide within the mRNA 5 ' cap influences protein production levels in a cell-specific manner. This modification can strongly hamper protein biosynthesis or have no influence on protein production levels, depending on the cell line. Interestingly, 2 '-O-methylation of the second transcribed nucleotide and the presence of m(6)A(m) as the first transcribed nucleotide serve as determinants that define transcripts as 'self' and contribute to transcript escape from the host innate immune response. Additionally, cap methylation status does not influence transcript affinity towards translation initiation factor eIF4E or in vitro susceptibility to decapping by DCP2; however, we observe the resistance of cap2-RNA to DXO (decapping exoribonuclease)-mediated decapping and degradation.

Key words

STRUCTURAL INSIGHTS/HUMAN IFIT1/TRANSLATION/METHYLATION/MECHANISMS/EXPRESSION/ANALOGS/BINDING/MEMBERS

引用本文复制引用

出版年

2022
Nucleic Acids Research

Nucleic Acids Research

SCI
ISSN：0305-1048
被引量5
参考文献量54
段落导航相关论文