Nucleotide modifications decrease innate immune response induced by synthetic analogs of snRNAs and snoRNAs

Grigory Stepanov, Evgenii Zhuravlev, Victoria Shender, Anna Nushtaeva, Evgenia Balakhonova, Elena Mozhaeva, Marat Kasakin, Vladimir Koval, Alexander Lomzov, Marat Pavlyukov, Irina Malyants, Mikhail Zhorov, Tatyana Kabilova, Elena Chernolovskaya, Vadim Govorun, Elena Kuligina, Dmitry Semenov, Vladimir Richter

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Short nuclear regulatory RNAs play a key role in the main stages of maturation of the precursors of the major RNA species. Small nuclear RNAs (snRNAs) form the core of the spliceosome and are responsible for the splicing of pre-mRNA molecules. Small nucleolar RNAs (snoRNAs) direct post-transcriptional modification of pre-rRNAs. A promising strategy for the development of non-coding RNA (ncRNAs) mimicking molecules is the introduction of modified nucleotides, which are normally present in natural ncRNAs, into the structure of synthetic RNAs. We have created a set of snoRNAs and snRNA analogs and studied the effect of base modifications, specifically, pseudouridine (Ψ) and 5-methylcytidine (m5 C), on the immune-stimulating and cytotoxic properties of these RNAs. Here, we performed a whole-transcriptome study of the influence of synthetic snoRNA analogs with various modifications on gene expression in human cells. Moreover, we confirmed the role of PKR in the recognition of snoRNA and snRNA analogs using the short hairpin RNA (shRNA) technique. We believe that the data obtained will contribute to the understanding of the role of nucleotide modification in ncRNA functions, and can be useful for creating the agents for gene regulation based on the structure of natural snoRNAs and snRNAs.

Original languageEnglish
Article number531
Number of pages18
JournalGenes
Volume9
Issue number11
DOIs
Publication statusPublished - 2 Nov 2018

Keywords

  • Innate immune response
  • PKR
  • RNA modification
  • RNA-seq
  • Small nuclear RNAs
  • Small nucleolar RNAs
  • Synthetic RNA analogs
  • ACTIVATION
  • STRANDED-RNA
  • SMALL NUCLEAR
  • small nuclear RNAs
  • RIBOSOMAL-RNA
  • small nucleolar RNAs
  • GENE
  • NONCODING RNAS
  • PSEUDOURIDINE
  • RNA-Seq
  • innate immune response
  • SMALL NUCLEOLAR RNAS
  • synthetic RNA analogs
  • 5'-TRIPHOSPHATE RNA
  • REVEALS

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