Implication of NMD inhibition by Rex to the host cell leukemogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 24501304
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Carcinogenesis
• Research Institution: The University of Tokyo
• Principal Investigator: NAKANO Kazumi 東京大学, 新領域創成科学研究科, 助教 (60549591)
• Co-Investigator(Kenkyū-buntansha): WATANABE Toshiki 東京大学, 大学院新領域創成科学研究科, 教授 (30182934)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ＨＴＬＶ－１ / Ｒｅｘ / ＮＭＤ / ＡＴＬ

Outline of Final Research Achievements

Nonsense-mediated mRNA decay (NMD) is a conserved cellular mRNA quality control mechanism. RNA signals to express viral genes potentially initiate NMD, nevertheless it is not clear how viruses evade NMD. Human-T-cell Leukemia Virus type-I (HTLV-1) is a retrovirus responsible for Adult T-cell Leukemia (ATL). Previously, we demonstrated that HTLV-1 Rex approves the stability of viral RNA by inhibiting NMD. In the present study, we focused on the molecular mechanism of NMD inhibition by Rex, and further clarified that the N-terminal region of Rex with unknown function (domain-X), was critical for effective suppression of NMD activity. We also showed that overexpression of Rex resulted in significant changes of more than 9,000 gene expression profiles in CEM human T cell line. Our results propose a possibility that Rex stabilizes the viral RNA by inhibition of NMD through the domain-X, and perturbs cellular mRNA metabolism and host cell homeostasis for its new function.

Free Research Field

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