TY - JOUR

T1 - Nucleotide modifications decrease innate immune response induced by synthetic analogs of snRNAs and snoRNAs

AU - Stepanov, Grigory

AU - Zhuravlev, Evgenii

AU - Shender, Victoria

AU - Nushtaeva, Anna

AU - Balakhonova, Evgenia

AU - Mozhaeva, Elena

AU - Kasakin, Marat

AU - Koval, Vladimir

AU - Lomzov, Alexander

AU - Pavlyukov, Marat

AU - Malyants, Irina

AU - Zhorov, Mikhail

AU - Kabilova, Tatyana

AU - Chernolovskaya, Elena

AU - Govorun, Vadim

AU - Kuligina, Elena

AU - Semenov, Dmitry

AU - Richter, Vladimir

N1 - Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2018/11/2

Y1 - 2018/11/2

N2 - 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.

AB - 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.

KW - Innate immune response

KW - PKR

KW - RNA modification

KW - RNA-seq

KW - Small nuclear RNAs

KW - Small nucleolar RNAs

KW - Synthetic RNA analogs

KW - ACTIVATION

KW - STRANDED-RNA

KW - SMALL NUCLEAR

KW - small nuclear RNAs

KW - RIBOSOMAL-RNA

KW - small nucleolar RNAs

KW - GENE

KW - NONCODING RNAS

KW - PSEUDOURIDINE

KW - RNA-Seq

KW - innate immune response

KW - SMALL NUCLEOLAR RNAS

KW - synthetic RNA analogs

KW - 5'-TRIPHOSPHATE RNA

KW - REVEALS

UR - http://www.scopus.com/inward/record.url?scp=85056573741&partnerID=8YFLogxK

U2 - 10.3390/genes9110531

DO - 10.3390/genes9110531

M3 - Article

C2 - 30400232

AN - SCOPUS:85056573741

VL - 9

JO - Genes

JF - Genes

SN - 2073-4425

IS - 11

M1 - 531

ER -