Murine leukemia virus (MLV) P50 protein induces cell transformation via transcriptional regulatory function

Retrovirology

Research

Nelly Godefroy¹  Khalid Belkhir¹  Jean-Marie Peloponese²  Marylene Mougel³  Sebastien Laine³  Jerome Feuillard³  Felipe Leon Diaz³  Charbel Akkawi³ 

[1] ISEM, CNRS, EPHE, Université Montpellier, IRD, Montpellier, France;Team APIR: IRIM, UMR9004, CNRS, University of Montpellier, Montpellier, France;Team R2D2: Retroviral RNA Dynamics and Delivery, IRIM, UMR9004, CNRS, University of Montpellier, Montpellier, France;

关键词: Retrovirus;    Murine leukemia virus;    SD’;    P50;    Cancerogenesis;    Leukemia;    Transcription regulation;    Transcriptomic;   

DOI  :  10.1186/s12977-023-00631-w

 received in 2023-04-10, accepted in 2023-08-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe murine leukemia virus (MLV) has been a powerful model of pathogenesis for the discovery of genes involved in cancer. Its splice donor (SD’)-associated retroelement (SDARE) is important for infectivity and tumorigenesis, but the mechanism remains poorly characterized. Here, we show for the first time that P50 protein, which is produced from SDARE, acts as an accessory protein that transregulates transcription and induces cell transformation.ResultsBy infecting cells with MLV particles containing SDARE transcript alone (lacking genomic RNA), we show that SDARE can spread to neighbouring cells as shown by the presence of P50 in infected cells. Furthermore, a role for P50 in cell transformation was demonstrated by CCK8, TUNEL and anchorage-independent growth assays. We identified the integrase domain of P50 as being responsible for transregulation of the MLV promoter using luciferase assay and RTqPCR with P50 deleted mutants. Transcriptomic analysis furthermore revealed that the expression of hundreds of cellular RNAs involved in cancerogenesis were deregulated in the presence of P50, suggesting that P50 induces carcinogenic processes via its transcriptional regulatory function.ConclusionWe propose a novel SDARE-mediated mode of propagation of the P50 accessory protein in surrounding cells. Moreover, due to its transforming properties, P50 expression could lead to a cellular and tissue microenvironment that is conducive to cancer development.

【 授权许可】

CC BY   
© Diane D. Jeang 2023

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