期刊
NUCLEIC ACIDS RESEARCH
卷 49, 期 18, 页码 10657-10676出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab787
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资金
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Ligue Contre le Cancer, comite du Rhone [PPE R15159CC]
- French Laboratory of Excellence project ECOFECT [ANR-11-LABX-0048]
- Deutsche Forschungsgemeinschaft [SFB1064/TP A13]
- Deutsche Krebshilfe [70112875]
- German Center for Infection Research [07.814]
- Institut National de la Sant 'e et de la Recherche M 'edicale
This study systematically analyzed the time-resolved expression of cellular mRNA splice variants during EBV infection of resting B lymphocytes. The results showed that major modifications in alternative splice variant expression occurred as early as day 1 post-infection, indicating that splicing regulation, in addition to transcription, provides an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation.
Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers worldwide. Ex vivo, the virus efficiently infects resting human B lymphocytes and induces their continuous proliferation. This process is accompanied by a global reprogramming of cellular gene transcription. However, very little is known on the impact of EBV infection on the regulation of alternative splicing, a pivotal mechanism that plays an essential role in cell fate determination and is often deregulated in cancer. In this study, we have developed a systematic time-resolved analysis of cellular mRNA splice variant expression during EBV infection of resting B lymphocytes. Our results reveal that major modifications of alternative splice variant expression appear as early as day 1 post-infection and suggest that splicing regulation provides-besides transcription-an additional mechanism of gene expression regulation at the onset of B cell activation and proliferation. We also report a role for the viral proteins, EBNA2 and EBNA-LP, in the modulation of specific alternative splicing events and reveal a previously unknown function for EBNA-LP-together with the RBM4 splicing factor-in the alternative splicing regulation of two important modulators of cell proliferation and apoptosis respectively, NUMB and BCL-X.
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