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Updated: Oct 13, 2025

Merkel Cell Polyomavirus Infection and Detection
13:45

Merkel Cell Polyomavirus Infection and Detection

Published on: February 7, 2019

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Merkel cell polyomavirus T-antigens regulate DICER1 mRNA stability and translation through HSC70

Jiwei Gao1, Hao Shi1, C Christofer Juhlin1,2

  • 1Department of Oncology-Pathology, Karolinska Institutet; BioClinicum, Karolinska University Hospital, 171 64 Solna, Sweden.

Iscience
|November 11, 2021
PubMed

Insights

Merkel cell polyomavirus T-antigens enhance microRNA production by increasing DICER1 protein and mRNA stability. This occurs through interaction with heat shock cognate 70 (HSC70), revealing a new mRNA regulation pathway.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Merkel cell carcinoma (MCC) is an aggressive skin cancer primarily caused by Merkel cell polyomavirus (MCPyV).
  • MCPyV T-antigens are known to influence microRNA (miRNA) expression, but the precise mechanism remains unclear.
  • DICER1 is a crucial enzyme in miRNA biogenesis, and its regulation is vital for cellular function.

Purpose of the Study:

  • To elucidate the mechanism by which MCPyV T-antigens regulate DICER1 expression and miRNA biogenesis.
  • To investigate the role of heat shock cognate 70 (HSC70) in mediating the interaction between MCPyV T-antigens and DICER1 mRNA.
  • To explore the broader implications of this interaction for mRNA regulation in MCPyV-infected cells.

Main Methods:

  • Investigated the interaction between MCPyV T-antigens, HSC70, and DICER1 mRNA using co-immunoprecipitation and reporter assays.
  • Assessed the impact of MCPyV T-antigen and HSC70 on DICER1 protein levels and mRNA stability.
  • Utilized luciferase reporter assays with AU-rich elements (AREs) to confirm the functional interaction.

Main Results:

  • MCPyV T-antigens increase DICER1 protein expression and mRNA stability.
  • HSC70 directly binds to AU-rich elements (AREs) within the DICER1 mRNA coding and 3' untranslated regions in the presence of MCPyV T-antigen.
  • The T-antigen/HSC70 complex enhances the activity of ARE-containing reporters and stabilizes ARE-containing mRNAs, suggesting a general role in mRNA regulation.

Conclusions:

  • MCPyV T-antigens utilize HSC70 to enhance DICER1 mRNA stability and protein expression, thereby promoting miRNA biogenesis.
  • This study reveals a novel mechanism of mRNA regulation involving the interaction of HSC70 with MCPyV T-antigens and ARE-containing mRNAs.
  • The findings suggest a broader role for MCPyV T-antigens in modulating cellular mRNA stability and translation through HSC70.
Keywords:
Immune responseImmunologyVirology

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