Welcome to Ariumi Project Laboratory





Members:
    
Yasuo Ariumi      Ph.D.     Associate Professor, PI    

Mikinori Ueno     Ph.D.     Postdoctoral researcher               

Rokeya Siddiqui            Graduate Student (D4)     

Hiroyuki Fukuda               Graduate Student (D1)         

Masato Nogawa                Undergraduate student (3rd grade) 
                    


Research Projects:

(1) Molecular mechanism of HIV-1 integration and LINE-1 retrotransposition.
(2) Role of RNA helicase and TRIM family in HIV-1, HBV, and LINE-1 life cycle.
(3) Role of RNA Granules (P-body and stress granules) and Nuclear boies in HIV-1, HBV, and LINE-1 life cycle.
(4) Identification and characterization of novel host factor(s) involved in HIV-1 life cycle.
RNA helicases and HIV-1 life cycle

RNA helicase plays an important role in host mRNA and viral mRNA transcription, transport, and translation. In deed, we have demonstrated that DDX3 and DDX6 are required for 
HCV RNA replication (Ariumi et alJ. Virol. 2007; Ariumi et alJ. Virol. 2011). Many viruses utilize RNA helicases in their life cycle, while HIV-1 does not encode an RNA 
helicase. Thus, host RNA helicase has been involved in HIV-1 replication. In this study, we have demonstrated that distinct DDX DEAD-box RNA helicases cooperate to modulate
the HIV-1 Rev and Tat function. We noticed that distinct DDX RNA helicases, including DDX1, DDX3, DDX5, DDX17, DDX21, DDX56, except DDX6, bound to the Rev 
protein and they colocalized with Rev in nucleolus or nucleus. In this context, these DEAD-box RNA helicases markedly enhanced the HIV-1 Rev-dependent RNA export. 
Furthermore, we have found that DDX3 is required for the HIV-1 Tat function. Notably, DDX3 colocalized and interacted with HIV-1 Tat in cytoplasmic foci. 
(Yasuda-Inoue et al. BBRC 2013a, b). 


Molecular mechanism of HIV-1 integration and host factor(s)

HIV-1 integration is an essential step for HIV-1 life cycle. We have investigated (1) how HIV-1 genome integrates into human genome, (2) which host factor(s) is required for HIV-1 integration, and (3) what happens after HIV-1 integration events, such as HIV-1 induced DNA damage and repair pathway or chromatin remodeling (Ariumi et alJ. Virol. 2005; Ariumi and Trono, J. Virol. 2006). HIV-1 generates dsDNA genome after reverse transcription. Such HIV-1 dsDNA might be recognized by and activate DNA damage sensor such as ATM kinase. This may facilitate HIV-1 integration into human genome. In addition, HIV-1 integration itself could induce dsDNA breaks in human genome and activate ATM signaling pathway resulting recruitment of several DNA repair machinery.    Furthermore, we also investigated INI-1/hSNF5 chromatin remodeling factor. INI1 was originally identified as an HIV-1 integrase-binding partner by Yeast-two hybrid screening. Notably, we have found that INI1 binds and enhances HIV-1 Tat-mediated transcription, suggesting that HIV-1 integration couples with initiation of HIV-1 transcription (Ariumi et alRetrovirology 2006).


P-body, Stress Granules, and HCV Infection

In this study, we have demonstrated for the first time that hepatitis C virus (HCV) hijacks the P-body and the stress granule components for HCV replication. In fact, HCV infection disrupted P-body formation of the microRNA effectors DDX3, DDX6, Lsm1, Xrn1, PATL1, and Ago2, but not the decapping enzyme DCP2, and dynamically redistributed these microRNA effectors to the HCV production factory around lipid droplets. Notably, HCV infection also induced stress granules 36h post-infection and redistributed the stress granule components G3BP1, ataxin-2, and poly(A)-binding protein 1 (PABP1) to the HCV production factory. Importantly, we found that these P-body and the stress granule components are required for the HCV life cycle (Ariumi et alJ. Virol. 2011). 

 Host factors involved in LINE-1 retrotransposition

Although LINE-1 is a genetic mobile element composing about 17% of the human genome, host factors involved in LINE-1 retrotransposition have not fully understood. In this study, we have demonstrated that MOV10 RNA helicase as well as APOBEC3G (A3G) significantly suppresses LINE-1 retrotransposition using EGFP-retrotransposition detector cassette. The fluorescence of GFP can be detected by flow cytometer only when LINE-1 retrotransposition has happened.




Selected Publications


1.
     Hepatitis C virus hijacks P-body and stress granule components around lipid droplets.
     Ariumi Y, Kuroki M, Kushima Y, Osugi K, Hijikata M, Maki M, Ikeda M, Kato N.
        J Virol. 2011 Jul;85(14):6882-92. doi: 10.1128/JVI.02418-10. Epub 2011 May 4.

   

2.

The ESCRT system is required for hepatitis C virus production.

Ariumi Y, Kuroki M, Maki M, Ikeda M, Dansako H, Wakita T, Kato N.

PLoS One. 2011 Jan 11;6(1):e14517. doi: 10.1371/journal.pone.0014517.

3.

Arsenic trioxide inhibits hepatitis C virus RNA replication through modulation of the glutathione redox system and oxidative stress.

Kuroki M, Ariumi Y, Ikeda M, Dansako H, Wakita T, Kato N.

J Virol. 2009 Mar;83(5):2338-48. doi: 10.1128/JVI.01840-08. Epub 2008 Dec 24.

4.

The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication.

Ariumi Y, Kuroki M, Dansako H, Abe K, Ikeda M, Wakita T, Kato N.

J Virol. 2008 Oct;82(19):9639-46. doi: 10.1128/JVI.00351-08. Epub 2008 Jul 30.    Selected as "F1000 Biology Must Read"  & "Spotlight" by editor

5.

DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication.

Ariumi Y, Kuroki M, Abe K, Dansako H, Ikeda M, Wakita T, Kato N.

J Virol. 2007 Dec;81(24):13922-6. Epub 2007 Sep 12.

6.

The integrase interactor 1 (INI1) proteins facilitate Tat-mediated human immunodeficiency virus type 1 transcription.

Ariumi Y, Serhan F, Turelli P, Telenti A, Trono D.

Retrovirology. 2006 Aug 5;3:47.

10.

Distinct nuclear body components, PML and SMRT, regulate the trans-acting function of HTLV-1 Tax oncoprotein.

Ariumi Y, Ego T, Kaida A, Matsumoto M, Pandolfi PP, Shimotohno K.

Oncogene. 2003 Mar 20;22(11):1611-9.

11.

The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression.

Ego T, Ariumi Y, Shimotohno K.

Oncogene. 2002 Oct 17;21(47):7241-6.

12.

HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration.

Ariumi Y, Kaida A, Lin JY, Hirota M, Masui O, Yamaoka S, Taya Y, Shimotohno K.

Oncogene. 2000 Mar 16;19(12):1491-9.

13.

Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein.

Kaida A, Ariumi Y, Ueda Y, Lin JY, Hijikata M, Ikawa S, Shimotohno K.

Oncogene. 2000 Feb 10;19(6):827-30.

14.

Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro.

Ariumi Y, Masutani M, Copeland TD, Mimori T, Sugimura T, Shimotohno K, Ueda K, Hatanaka M, Noda M.

Oncogene. 1999 Aug 12;18(32):4616-25.

15.

Novel internal promoter/enhancer of HTLV-I for Tax expression.

Nosaka T, Ariumi Y, Sakurai M, Takeuchi R, Hatanaka M.

Nucleic Acids Res. 1993 Nov 11;21(22):5124-9.

 Collaborators

Dr. Didier Trono       Ecole Polytechnique Fédérale de Lausanne (EPFL) 

Dr. Priscilla Turelli   Ecole Polytechnique Fédérale de Lausanne (EPFL) 


Dr. Wenfeng An        South Dakota State University


Position of Graduate Student:


Ariumi Project Laboratory invites graduate school students.

http://www.medphas.kumamoto-u.ac.jp/en/medgrad/admissions/index.html


Contact Us:


Yasuo Ariumi, Ph.D. Associate Professor

2-2-1 Honjo, 

Kumamoto 860-0811

Japan


Phone and Fax: +81-96-373-6834

E-mail: ariumi@kumamoto-u.ac.jp

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