The accumulation of influenza A virus segment 7 spliced mRNAs is regulated by the NS1 protein

Nicole C Robb1, Ervin Fodor1

  • 1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.

Insights

The influenza A virus NS1 protein regulates the splicing of M1 mRNA. This regulation is dependent on NS1's RNA-binding ability, impacting viral gene expression.

Area of Science:

  • Virology
  • Molecular Biology
  • Gene Expression

Background:

  • Influenza A virus M1 mRNA undergoes alternative splicing to produce various mRNA forms.
  • Both spliced and unspliced mRNAs encode functional proteins, indicating regulated splicing.

Purpose of the Study:

  • To investigate the role of the influenza A virus NS1 protein in the regulation of M1 mRNA splicing.
  • To determine if NS1's RNA-binding ability is crucial for its effect on splicing.

Main Methods:

  • Utilized radioactively labeled primers to track spliced and unspliced M segment mRNAs.
  • Employed viral infection and ribonucleoprotein (RNP) reconstitution assays.
  • Assessed the impact of NS1 protein co-expression on mRNA accumulation.

Main Results:

  • Co-expression of the NS1 protein significantly altered the accumulation of spliced M1 mRNAs in RNP reconstitution assays.
  • The observed effect of NS1 on splicing was dependent on its RNA-binding capability.
  • Un-spliced and spliced M segment mRNAs accumulation was modulated by NS1.

Conclusions:

  • The influenza A virus NS1 protein plays a regulatory role in the alternative splicing of M1 mRNA.
  • NS1's RNA-binding activity is essential for its function in modulating M1 mRNA splicing.
  • These findings highlight a novel mechanism of viral gene expression control by NS1.

Related Concept Videos

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 stands for...
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
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 ATP-dependent...
Coronavirus01:29

Coronavirus

Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...