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Related Concept Videos

RNA Interference01:23

RNA Interference

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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...
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siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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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...
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MicroRNAs01:22

MicroRNAs

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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...
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Experimental RNAi02:15

Experimental RNAi

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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...
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Types of RNA01:23

Types of RNA

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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...
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Riboswitches01:56

Riboswitches

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
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Updated: Sep 17, 2025

Visualization of SARS-CoV-2 using Immuno RNA-Fluorescence In Situ Hybridization
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SARS-CoV-2 RNA-binding protein suppresses extracellular miRNA release.

Hyejin Mun1, Chang Hoon Shin1, Qingxuan Fei2

  • 1Department of Oncology Science, University of Oklahoma, Oklahoma City, OK, USA.

RNA Biology
|July 1, 2025
PubMed
Summary

SARS-CoV-2 RNA-binding proteins (RBPs) hijack host RNA metabolism. Nsp9 protein suppresses antiviral responses by inhibiting miRNA let-7b release and activity, impacting Toll-like Receptor 7 (TLR7) signaling.

Keywords:
Nsp9POLR2DSARS-CoV-2let-7bmiRNA

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Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • The COVID-19 pandemic is caused by SARS-CoV-2, a betacoronavirus.
  • While the SARS-CoV-2 genome is known, the functions of its individual proteins remain largely uncharacterized.
  • Understanding viral protein functions is crucial for developing effective therapeutics.

Purpose of the Study:

  • To investigate the function of SARS-CoV-2 RNA-binding proteins (RBPs).
  • To determine the interaction between SARS-CoV-2 RBPs and host RNA metabolism, specifically miRNA let-7b.
  • To elucidate the mechanism by which SARS-CoV-2 proteins modulate antiviral responses via Toll-like Receptor 7 (TLR7).

Main Methods:

  • Biochemical and molecular biology techniques were employed.
  • Nuclear Magnetic Resonance (NMR) spectroscopy was used to identify protein-ligand interactions.
  • Assays were performed to assess gene expression, miRNA release, and TLR7 activity.

Main Results:

  • Four SARS-CoV-2 RBPs were found to regulate host RNA metabolism through direct interaction with mature miRNA let-7b.
  • The SARS-CoV-2 RBP Nsp9 primarily binds miRNA let-7b, a ligand of TLR7.
  • Nsp9 suppresses host gene expression by promoting let-7b-mediated silencing of POLR2D and inhibits extracellular let-7b release, thereby dampening antiviral activity via TLR7.

Conclusions:

  • SARS-CoV-2 hijacks host RNA metabolism to suppress antiviral responses and cellular transcription.
  • The viral protein Nsp9 plays a key role in inhibiting let-7b's antiviral activity through TLR7.
  • These findings provide insights into SARS-CoV-2 pathogenesis and potential therapeutic targets, particularly concerning TLR7 modulation.