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

Jiwei Gao; Hao Shi; C Christofer Juhlin; Catharina Larsson; Weng-Onn Lui

doi:10.1016/j.isci.2021.103264

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

iScience. 2021 Oct 14;24(11):103264. doi: 10.1016/j.isci.2021.103264. eCollection 2021 Nov 19.

Authors

Jiwei Gao¹, Hao Shi¹, C Christofer Juhlin^{1

2}, Catharina Larsson¹, Weng-Onn Lui¹

Affiliations

¹ Department of Oncology-Pathology, Karolinska Institutet; BioClinicum, Karolinska University Hospital, 171 64 Solna, Sweden.
² Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, 171 64 Solna, Sweden.

Abstract

Merkel cell carcinoma is an aggressive skin malignancy, mostly caused by Merkel cell polyomavirus (MCPyV). MCPyV T-antigens can induce mature microRNA expressions through the DnaJ domain, but its underlying mechanism is still unknown. Here, we report that the T-antigens induce protein expression and mRNA stability of DICER1, a key factor in microRNA biogenesis, through heat shock cognate 70 (HSC70). HSC70 directly interacts with the AU-rich elements (ARE) of DICER1 mRNA in both coding and 3' untranslated region in the presence of MCPyV T-antigen. The T-antigen/HSC70 interaction could induce luciferase activity of synthetic ARE-containing reporter, as well as the stability of ARE-containing mRNAs, suggesting a broader role of MCPyV T-antigens in regulating multiple mRNAs via HSC70. These findings highlight a new role for the interaction of HSC70 and MCPyV T-antigens in mRNA regulation and an undescribed regulatory mechanism of DICER1 mRNA stability and translation through its direct interaction with HSC70.

Keywords: Immune response; Immunology; Virology.