Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells

Davide Barbagallo1, Concetta Ilenia Palermo2, Cristina Barbagallo3

  • 1Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics Giovanni Sichel, University of Catania, 95123, Catania, Italy. dbarbaga@unict.it.

Insights

A novel circular RNA (circRNA), circ_3205, synthesized by SARS-CoV-2, was identified in COVID-19 patients. This viral circRNA acts as a ceRNA, sponging miR-298 and upregulating KCNMB4 and PRKCE mRNA involved in immune response.

Area of Science:

  • Virology
  • Molecular Biology
  • Genomics

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19.
  • Circular RNAs (circRNAs) are emerging as critical regulators in various biological processes.
  • Understanding viral-host interactions at the molecular level is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To identify and characterize SARS-CoV-2-synthesized circRNAs.
  • To investigate the role of a specific viral circRNA, circ_3205, in host cells.
  • To explore the potential mechanism of circ_3205 as a competing endogenous RNA (ceRNA).

Main Methods:

  • Identification of circ_3205 using VirusCircBase.
  • Expression analysis of circRNAs, miRNAs, and mRNA targets via real-time PCR in patient samples.
  • Prediction of circRNA-miRNA interactions using TarpMiR, ACT, and STarMir tools.
  • Analysis of biological processes and miRNA targets using DIANA miRPath v3.0.

Main Results:

  • SARS-CoV-2 circ_3205 was exclusively detected in infected individuals and correlated positively with viral load and Spike (S) mRNA levels.
  • Human miR-298 was predicted to interact with circ_3205, targeting KCNMB4 and PRKCE mRNAs.
  • KCNMB4 and PRKCE mRNA levels were upregulated in positive samples and correlated with circ_3205 expression.

Conclusions:

  • SARS-CoV-2 circ_3205 is synthesized upon host cell infection.
  • circ_3205 functions as a ceRNA, sequestering hsa-miR-298.
  • This mechanism contributes to the upregulation of KCNMB4 and PRKCE, potentially impacting blood coagulation and immune response in COVID-19 patients.

Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
17.2K
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.6K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.3K
Small interfering RNAs (siRNA)02:30

Small interfering RNAs (siRNA)

3.8K
lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
9.0K
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.3K