Details of the Researcher

PHOTO

Raja Norazireen Binti Raja Ahmad
Section
Institute of Development, Aging and Cancer
Job title
Assistant Professor
Degree

  • Doctor of Philosophy, Medical Science (Kumamoto University)

e-Rad No.
50999761

Research History 7

  • 2024/04 - Present
    Institute of Development, Aging and Cancer, Tohoku University

  • 2022/04 - 2024/03
    Institute of Development, Aging and Cancer, Tohoku University

  • 2017/09 - 2022/03
    Graduate School of Medical Sciences, Kumamoto University

  • 2015/04 - 2017/04
    Cell Therapy Centre, Universiti Kebangsaan Malaysia Medical Centre

  • 2013/07 - 2015/03
    Virtuallux Sdn Bhd

  • 2012/01 - 2013/06
    Inno Bio Diagnostics Sdn Bhd

  • 2008/07 - 2011/12
    Inno Bio Diagnostics Sdn Bhd

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Education 3

  • Graduate School of Medical Sciences, Kumamoto University

    2018/04 - 2022/03

  • Graduate School of Science and Engineering for Education, University of Toyama

    2006/04 - 2008/03

  • Faculty of Engineering, University of Toyama

    2002/04 - 2006/03

Papers 4

  1. Pathological mutations promote proteolysis of mitochondrial tRNA-specific 2-thiouridylase 1 (MTU1) via mitochondrial caseinolytic peptidase (CLPP)

    Raja Norazireen Raja Ahmad, Long-Teng Zhang, Rikuri Morita, Haruna Tani, Yong Wu, Takeshi Chujo, Akiko Ogawa, Ryuhei Harada, Yasuteru Shigeta, Kazuhito Tomizawa, Fan-Yan Wei

    Nucleic Acids Research　52　(3)　1341-1358　2023/12/19

    Publisher: Oxford University Press (OUP)

    DOI： 10.1093/nar/gkad1197 　

    ISSN： 0305-1048

    eISSN： 1362-4962

    More details Close

    Abstract MTU1 controls intramitochondrial protein synthesis by catalyzing the 2-thiouridine modification of mitochondrial transfer RNAs (mt-tRNAs). Missense mutations in the MTU1 gene are associated with life-threatening reversible infantile hepatic failure. However, the molecular pathogenesis is not well understood. Here, we investigated 17 mutations associated with this disease, and our results showed that most disease-related mutations are partial loss-of-function mutations, with three mutations being particularly severe. Mutant MTU1 is rapidly degraded by mitochondrial caseinolytic peptidase (CLPP) through a direct interaction with its chaperone protein CLPX. Notably, knockdown of CLPP significantly increased mutant MTU1 protein expression and mt-tRNA 2-thiolation, suggesting that accelerated proteolysis of mutant MTU1 plays a role in disease pathogenesis. In addition, molecular dynamics simulations demonstrated that disease-associated mutations may lead to abnormal intermolecular interactions, thereby impairing MTU1 enzyme activity. Finally, clinical data analysis underscores a significant correlation between patient prognosis and residual 2-thiolation levels, which is partially consistent with the AlphaMissense predictions. These findings provide a comprehensive understanding of MTU1-related diseases, offering prospects for modification-based diagnostics and novel therapeutic strategies centered on targeting CLPP.

  2. Regulation of mitochondrial iron homeostasis by sideroflexin 2

    Ei Ei Mon, Fan-Yan Wei, Raja Norazireen Raja Ahmad, Takahiro Yamamoto, Toshiro Moroishi, Kazuhito Tomizawa

    The Journal of Physiological Sciences　69　(2)　359-373　2018/12/20

    Publisher: Springer Science and Business Media LLC

    DOI： 10.1007/s12576-018-0652-2 　

    ISSN： 1880-6546

    eISSN： 1880-6562

  3. Establishment of Stable and Secretable TATκ-GFP Recombinant Protein: A Preliminary Report of Promoter Methylation in 293T Cell Line

    Zariyantey Abd Hamid, Fazlina Nordin, Raja Norazireen Raja Ahmad, Balqis Mat Rashid, Ubashini Vijakumaran

    Sains Malaysiana　47　(10)　2473-2480　2018/10/31

    Publisher: Penerbit Universiti Kebangsaan Malaysia (UKM Press)

    DOI： 10.17576/jsm-2018-4710-24 　

    ISSN： 0126-6039

  4. Transactivator protein: An alternative for delivery of recombinant proteins for safer reprogramming of induced Pluripotent Stem Cell

    Fazlina Nordin, Raja Norazireen Raja Ahmad, Farzin Farzaneh

    Virus Research　235　106-114　2017/05

    Publisher: Elsevier BV

    DOI： 10.1016/j.virusres.2017.04.007 　

    ISSN： 0168-1702

Presentations 1

  1. Supersulfide in RNA modification and metabolic diseases Invited

    Raja Norazireen Raja Ahmad

    1st International G-ReXs Conference, April 2024

Research Projects 1

  1. Mechanism of mitochondrial translation regulation and quality management

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Research Activity Start-up

    Institution: Tohoku University

    2024/07/31 - 2026/03/31