A potential role for SARS-CoV-2 small viral RNAs in targeting host microRNAs and modulating gene expression

Zachary T Neeb1, Alexander J Ritter2, Lokendra V Chauhan3

  • 1Department of Molecular, Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California Santa Cruz, Santa Cruz, CA, USA.

Scientific Reports
|December 15, 2022
PubMed

Insights

This study reveals novel small viral RNAs (svRNAs) produced by SARS-CoV-2 that interact with host gene expression. These svRNAs may influence viral propagation and offer potential therapeutic targets for COVID-19.

Area of Science:

  • Molecular Biology
  • Virology
  • Genomics

Background:

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, but its impact on host RNA machinery is unclear.
  • Understanding viral-host interactions at the molecular level is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the effects of SARS-CoV-2 infection on host mRNA and small RNA (sRNA) expression.
  • To identify and characterize SARS-CoV-2-derived small viral RNAs (svRNAs) and their potential interactions with host molecules.

Main Methods:

  • Comparative transcriptomics analysis of infected human lung (Calu-3) and monkey kidney (Vero-E6) cell lines.
  • Identification and sequencing of host and viral small RNAs.
  • Bioinformatic prediction of interactions between svRNAs and host mRNAs/miRNAs.

Main Results:

  • SARS-CoV-2 infection caused global changes in host gene expression and differential expression of host microRNAs (miRNAs).
  • Over a hundred novel svRNAs were discovered, originating from various viral genome regions via a non-canonical pathway.
  • A significant number of svRNAs were predicted to interact with differentially expressed host miRNAs and mRNAs, suggesting a role in post-transcriptional regulation.

Conclusions:

  • SARS-CoV-2 infection profoundly alters host gene expression and produces unique svRNAs.
  • These svRNAs may modulate host post-transcriptional gene regulation, potentially aiding viral propagation.
  • Targeting these svRNAs could represent a novel therapeutic strategy against COVID-19.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.1K
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...
16.9K
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...
26.3K
Translational Regulation01:29

Translational Regulation

Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
72
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...
6.2K
Types of RNA01:23

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
64.3K