Shiomi, Haruhiko

写真a

Affiliation

School of Medicine, Department of Molecular Biology (Shinanomachi)

Position

Professor

Related Websites

External Links

Profile 【 Display / hide

  • Haruhiko Siomi is Professor in the Department of Molecular Biology at Keio University School of Medicine. He obtained his Diploma degree (1982) and M.S. degree (1984) in Agricultural Chemistry from Gifu University, and his Ph. D. (1988) in Virology from Kyoto University. He was then an HHMI associate with Gideon Dreyfuss at the University of Pennsylvania School of Medicine, where he studied RNA-binding proteins, such as hnRNP proteins and FMR1. He joined the University of Tokushima faculty in 1999, where he started to work on RNA silencing. In 2008, he moved to his current position at Keio University. His research focuses on many aspects of RNA silencing including small RNA biogenesis, transposon silencing, and roles of Argonautes/Piwis in silencing.

Profile Summary 【 Display / hide

  • Lab website: http://siomilab.med.keio.ac.jp/

Academic Background 【 Display / hide

  • 1984.04
    -
    1988.03

    Kyoto University, Kyoto University, Kyoto University

    Graduate School, Completed, Doctoral course

Academic Degrees 【 Display / hide

  • 医学博士 , Kyoto University, Coursework, 1988.03

    Two Major Subgroups of Human T-cell Leukemia Virus Type 1 in Japan

 

Research Areas 【 Display / hide

  • Life Science / Genome biology

  • Life Science / Genetics

Research Keywords 【 Display / hide

  • RNAi, RNA silencing, small RNA, transposable elements, epigenetic modifications

  • germ line cells

Research Themes 【 Display / hide

  • Understanding of how transposable elements are integrated into cellular functions, 

    2016
    -
    Present

  • Understanding of how transposable elements are repressed, 

    2000
    -
    Present

     View Summary

    Our laboratory is investigating RNA silencing pathways, in which cognate RNA targets are inactivated by small RNA–Argonaute complexes. Key steps in the RNA silencing pathway are shared by a diverse set of gene regulatory mechanisms. These include mechanisms that silence endogenous genes, particularly genes involved in development and stem cell maintenance, and mechanisms that restrain the expression of transposable elements (TEs) or viruses and direct transcriptional gene silencing.

 

Papers 【 Display / hide

  • Human PIWI (HIWI) is an azoospermia factor

    Hasuwa Hidetoshi, Ishino Kyoko, Siomi Haruhiko

    Science China Life Sciences    1 - 3 2017.08

    ISSN  1674-7305

  • Deep sequencing and high-throughput analysis of PIWI-associated small RNAs

    Iwasaki Yuka W., Ishino Kyoko, Siomi Haruhiko

    Methods  2017.03

    ISSN  1046-2023

     View Summary

    <p>Small RNAs are now known to be major regulatory factors of gene expression. Emerging methods based on deep-sequencing have enabled the analysis of small RNA expression in a high-throughput manner, leading to the identification of large numbers of small RNAs in various species. Moreover, profiling small RNA data together with transcriptome data enables transcriptional and post-transcriptional regulation mediated by small RNAs to be hypothesized. Here, we isolated PIWIL1 (MIWI)-associated small RNAs from mouse testes, and performed small RNA-seq analysis. In addition, directional RNA-seq was performed using Piwil1 mutant mouse testes. Using these data, we describe protocols for analyzing small RNA-seq reads to obtain profiles of small RNAs associated with PIWI proteins. We also present bioinformatic protocols for analyzing RNA-seq reads that aim to annotate expression of piRNA clusters and identify genes regulated by piRNAs.</p>

  • Mobile elements control stem cell potency

    Hasuwa Hidetoshi, Siomi Haruhiko

    Science 355 ( 6325 ) 581 - 582 2017.02

    ISSN  0036-8075

  • Identification of mouse piRNA pathway components using anti-MIWI2 antibodies

    Hirano Takamasa, Hasuwa Hidetoshi, Siomi Haruhiko

      205 - 216 2017

     View Summary

    <p>The mouse testis has served as a popular model system to study a wide range of biological processes, including germcell development, meiosis, epigenetic changes of chromatin, transposon silencing, and small RNA-mediated epigenetic modifications. PIWI-interacting RNAs (piRNAs) are a class of small RNAs that are almost exclusively expressed in animal gonads. They repress transposons by forming effector complexes with PIWI proteins to maintain genome integrity of the germline. Here we describe detailed procedures of how to produce monoclonal antibodies against a mouse nuclear PIWI protein, MIWI2, which functions in de novo DNA methylation of target transposon loci. We then describe how to use the antibodies to isolate associated complexes and to detect MIWI2 immunohistochemically.</p>

  • Crystal Structure of Silkworm PIWI-Clade Argonaute Siwi Bound to piRNA

    Matsumoto Naoki, Nishimasu Hiroshi, Sakakibara Kazuhiro, Nishida Kazumichi M., Hirano Takamasa, Ishitani Ryuichiro, Siomi Haruhiko, Siomi Mikiko C., Nureki Osamu

    Cell 167 ( 2 ) 484 - 497.e9 2016.10

    ISSN  0092-8674

     View Summary

    <p>PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs) and silence transposable elements in animal gonads. Here, we report the crystal structure of a silkworm PIWI-clade Argonaute, Siwi, bound to the endogenous piRNA, at 2.4 Å resolution. Siwi adopts a bilobed architecture consisting of N-PAZ and MID-PIWI lobes, in which the 5′ and 3′ ends of the bound piRNA are anchored by the MID-PIWI and PAZ domains, respectively. A structural comparison of Siwi with AGO-clade Argonautes reveals notable differences in their nucleic-acid-binding channels, likely reflecting the distinct lengths of their guide RNAs and their mechanistic differences in guide RNA loading and cleavage product release. In addition, the structure reveals that Siwi and prokaryotic, but not eukaryotic, AGO-clade Argonautes share unexpected similarities, such as metal-dependent 5′-phosphate recognition and a potential structural transition during the catalytic-tetrad formation. Overall, this study provides a critical starting point toward a mechanistic understanding of piRNA-mediated transposon silencing.</p>

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Papers, etc., Registered in KOARA 【 Display / hide

Research Projects of Competitive Funds, etc. 【 Display / hide

  • 転移因子と初期胚の相互作用解析を通した全能性プログラムの解明

    2019.06
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research on Innovative Areas, Principal investigator

  • Molecular pathways leading to epigenome formation in mammalian germ cells

    2013.05
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (S), Principal investigator

Awards 【 Display / hide

  • FRAXA Research Foundation Award

    2003

    Type of Award: International academic award (Japan or overseas)

  • Cure Autism Now (CAN) Foundation Pilot Research Award

    2000

  • FRAXA Research Foundation Award

    Haruhiko Siomi, 1999

    Type of Award: International academic award (Japan or overseas)

  • MRDDRC (Mental Retardation and Developmental Disabilities  Research Center) Young Investigator Award

    Haruhiko Siomi, 1998

    Type of Award: International academic award (Japan or overseas)

 

Courses Taught 【 Display / hide

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2024

  • MOLECULAR BIOLOGY: SEMINAR

    2024

  • MOLECULAR BIOLOGY: PRACTICE

    2024

  • MOLECULAR BIOLOGY AND GENETIC MEDICINE

    2024

  • MOLECULAR BIOLOGY 2

    2024

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Courses Previously Taught 【 Display / hide

  • Basic Molecular Biology

    Keio University

    2017.04
    -
    2018.03

    Autumn Semester, Lecture

  • Basic Molecular Biology

    Keio University

    2017.04
    -
    2018.03

    Spring Semester, Lecture

  • MCBI

    Keio University

    2015.04
    -
    2016.03

    Autumn Semester, Lecture, 110people

  • MCBII

    Keio University

    2015.04
    -
    2016.03

    Spring Semester, Lecture, Within own faculty, 110people

  • Molecular biology/Human molecular genetics

    Keio University

    2015.04
    -
    2016.03

    Spring Semester, Within own faculty, 110people

Educational Activities and Special Notes 【 Display / hide

  • MCBI

    2013
    -
    Present

    , Device of Educational Contents

  • MCBII

    2008
    -
    Present

    , Device of Educational Contents

  • Molecular biology/human molecular genetics

    2008
    -
    Present

    , Device of Educational Contents

 

Social Activities 【 Display / hide

  • Associate member, Science Council of Japan

    2017
    -
    Present
  • Program Officer of the Research Center for Science Systems, JSPS

    2016
    -
    Present
  • Member of the 2014 Japan Prize Selection Committee for the Life Science field

    2013
    -
    2014
  • Scientific advisory committee for Ministry of Education, Culture, Sports, Science and Technology-Japan

    2012
    -
    2016
  • Advisory Board of National Institute for Basic Biology

    2009
    -
    2013

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Memberships in Academic Societies 【 Display / hide

  • The Molecular Biology Society of Japan, 

    2000
    -
    Present
  • The RNA Society of Japan, 

    2000
    -
    Present
  • The RNA Society, 

    1993
    -
    Present

Committee Experiences 【 Display / hide

  • 2013
    -
    2016

    住友財団「基礎科学研究助成事業」選考委員会委員, 住友財団「基礎科学研究助成事業」選考委員会

  • 2013
    -
    2014

    日本国際賞審査委員会委員, 日本国際賞審査委員会

  • 2012
    -
    2016

    科学官 , 文部科学省

  • 2012
    -
    2014

    研究評価委員会ヒトゲノム部会委員, かずさDNA研究所

  • 2009
    -
    2013

    自然科学研究機構・基礎生物学研究所 運営会議 委員, 自然科学研究機構・基礎生物学研究所 

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