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Modulation of mRNA 3'-End Processing and Transcription Termination in Virus-Infected Cells

Aarthi Vijayakumar1, Annsea Park2, Joan A Steitz1

  • 1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, United States.

Frontiers in Immunology
|February 28, 2022
PubMed

Insights

Viruses disrupt eukaryotic mRNA 3´-end processing, affecting gene expression and host antiviral responses. This viral interference leads to altered transcript levels and host shutoff, impacting cellular machinery.

Area of Science:

  • Molecular Biology
  • Virology
  • Gene Expression Regulation

Background:

  • Eukaryotic mRNA 3´-end processing involves pre-mRNA cleavage and polyadenylation, crucial for gene expression.
  • Disruption of this process affects mature mRNA levels and is implicated in viral infections.
  • Viral proteins can interfere with 3´-end processing machinery, leading to altered transcript levels and host shutoff.

Purpose of the Study:

  • To investigate the role of viral interference with eukaryotic mRNA 3´-end processing.
  • To understand how viruses modulate host gene expression and antiviral responses through 3´-end processing disruption.
  • To explore the mechanisms by which viruses utilize read-through transcripts.

Main Methods:

  • Analysis of viral protein interactions with host 3´-end processing factors.
  • Quantification of mature mRNA levels and read-through transcripts in infected cells.
  • Assessment of host shutoff and antiviral response suppression.

Main Results:

  • Viral proteins inhibit pre-mRNA cleavage and polyadenylation, causing read-through transcription.
  • Disrupted 3´-end processing leads to decreased mature mRNA levels and suppressed antiviral responses.
  • Read-through transcripts exhibit decreased polyadenylation, nuclear retention, and reduced translation.

Conclusions:

  • Viral modulation of host 3´-end processing is a key mechanism for viral pathogenesis and host immune evasion.
  • Viruses exploit read-through transcripts to manipulate host protein production and cellular functions.
  • Understanding these viral strategies is crucial for developing antiviral therapies.
Keywords:
downstream-of-gene transcriptsmRNA 3'-end processingread-through transcriptiontranscription terminationvirus-infected cells

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