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  1. Article: Retrotransposon renaissance in early embryos.

    Guo, Youjia / Li, Ten D / Modzelewski, Andrew J / Siomi, Haruhiko

    Trends in genetics : TIG

    2023  Volume 40, Issue 1, Page(s) 39–51

    Abstract: Despite being the predominant genetic elements in mammalian genomes, retrotransposons were often dismissed as genomic parasites with ambiguous biological significance. However, recent studies reveal their functional involvement in early embryogenesis, ... ...

    Abstract Despite being the predominant genetic elements in mammalian genomes, retrotransposons were often dismissed as genomic parasites with ambiguous biological significance. However, recent studies reveal their functional involvement in early embryogenesis, encompassing crucial processes such as zygotic genome activation (ZGA) and cell fate decision. This review underscores the paradigm shift in our understanding of retrotransposon roles during early preimplantation development, as well as their rich functional reservoir that is exploited by the host to provide cis-regulatory elements, noncoding RNAs, and functional proteins. The rapid advancement in long-read sequencing, low input multiomics profiling, advanced in vitro systems, and precise gene editing techniques encourages further dissection of retrotransposon functions that were once obscured by the intricacies of their genomic footprints.
    MeSH term(s) Animals ; Retroelements/genetics ; Genome ; Zygote ; Embryonic Development/genetics ; Mammals/genetics
    Chemical Substances Retroelements
    Language English
    Publishing date 2023-11-08
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 619240-3
    ISSN 1362-4555 ; 0168-9525 ; 0168-9479
    ISSN (online) 1362-4555
    ISSN 0168-9525 ; 0168-9479
    DOI 10.1016/j.tig.2023.10.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: It's time to exploit your favorite quirky organism with new technologies.

    Siomi, Haruhiko

    EMBO reports

    2014  Volume 15, Issue 6, Page(s) 620–621

    MeSH term(s) Computational Biology/methods ; Computational Biology/trends ; Developmental Biology/methods ; Developmental Biology/trends ; Genomics/methods ; Genomics/trends ; Models, Animal
    Language English
    Publishing date 2014-05-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201438955
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines.

    Murano, Kensaku / Guo, Youjia / Siomi, Haruhiko

    Biochemical Society transactions

    2021  Volume 49, Issue 6, Page(s) 2879–2890

    Abstract: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost ... ...

    Abstract The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost their lives. Various monoclonal antibodies of human origin that neutralize the SARS-CoV-2 infection have been isolated from convalescent patients for therapeutic and prophylactic purposes. Several vaccines have been developed to restrict the spread of the virus and have been rapidly administered. However, the rollout of vaccines has coincided with the spread of variants of concern. Emerging variants of SARS-CoV-2 present new challenges for therapeutic antibodies and threaten the efficacy of current vaccines. Here, we review the problems faced by neutralizing antibodies and vaccines in the midst of the increasing spread of mutant viruses.
    MeSH term(s) Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/therapeutic use ; Antibodies, Viral/immunology ; Antibodies, Viral/therapeutic use ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/therapeutic use ; Humans ; Pandemics/prevention & control ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Spike Glycoprotein, Coronavirus/immunology
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-12-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20210859
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  4. Article ; Online: Mobile elements control stem cell potency.

    Hasuwa, Hidetoshi / Siomi, Haruhiko

    Science (New York, N.Y.)

    2017  Volume 355, Issue 6325, Page(s) 581–582

    MeSH term(s) DNA Transposable Elements ; Humans ; Stem Cells
    Chemical Substances DNA Transposable Elements
    Language English
    Publishing date 2017--10
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aam6589
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  5. Article ; Online: RNA. Phased piRNAs tackle transposons.

    Siomi, Haruhiko / Siomi, Mikiko C

    Science (New York, N.Y.)

    2015  Volume 348, Issue 6236, Page(s) 756–757

    MeSH term(s) Animals ; Argonaute Proteins/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/enzymology ; Drosophila melanogaster/metabolism ; Endoribonucleases/metabolism ; Female ; Male ; Peptide Initiation Factors/metabolism ; RNA Cleavage ; RNA, Small Interfering/metabolism ; Retroelements ; Transcription, Genetic ; RNA, Guide, CRISPR-Cas Systems
    Chemical Substances Argonaute Proteins ; Drosophila Proteins ; Peptide Initiation Factors ; RNA, Small Interfering ; Retroelements ; Endoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2015-04-14
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aab3004
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  6. Article ; Online: TDP-43 safeguards the embryo genome from L1 retrotransposition.

    Li, Ten D / Murano, Kensaku / Kitano, Tomohiro / Guo, Youjia / Negishi, Lumi / Siomi, Haruhiko

    Science advances

    2022  Volume 8, Issue 47, Page(s) eabq3806

    Abstract: Transposable elements (TEs) are genomic parasites that propagate within the host genome and introduce mutations. Long interspersed nuclear element-1 (LINE-1 or L1) is the major TE class, which occupies nearly 20% of the mouse genome. L1 is highly active ... ...

    Abstract Transposable elements (TEs) are genomic parasites that propagate within the host genome and introduce mutations. Long interspersed nuclear element-1 (LINE-1 or L1) is the major TE class, which occupies nearly 20% of the mouse genome. L1 is highly active in mammalian preimplantation embryos, posing a major threat to genome integrity, but the mechanism of stage-specific protection against L1 retrotransposition is unknown. Here, we show that TAR DNA-binding protein 43 (TDP-43), mutations in which constitute a major risk factor for amyotrophic lateral sclerosis, inhibits L1 retrotransposition in mouse embryonic stem cells (mESCs) and preimplantation embryos. Knockdown of TDP-43 resulted in massive genomic L1 expansion and impaired cell growth in preimplantation embryos and ESCs. Functional analysis demonstrated that TDP-43 interacts with L1 open reading frame 1 protein (L1 ORF1p) to mediate genomic protection, and loss of this interaction led to derepression of L1 retrotransposition. Our results identify TDP-43 as a guardian of the embryonic genome.
    MeSH term(s) Animals ; Mice ; DNA-Binding Proteins/genetics ; Embryo, Mammalian ; Long Interspersed Nucleotide Elements ; Mammals/genetics ; Mouse Embryonic Stem Cells ; Open Reading Frames ; Retroelements
    Chemical Substances DNA-Binding Proteins ; TDP-43 protein, mouse ; Retroelements
    Language English
    Publishing date 2022-11-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abq3806
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Transcription of MERVL retrotransposons is required for preimplantation embryo development.

    Sakashita, Akihiko / Kitano, Tomohiro / Ishizu, Hirotsugu / Guo, Youjia / Masuda, Harumi / Ariura, Masaru / Murano, Kensaku / Siomi, Haruhiko

    Nature genetics

    2023  Volume 55, Issue 3, Page(s) 484–495

    Abstract: Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage ... ...

    Abstract Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) is transiently upregulated at the two-cell stage during ZGA. Although MERVL expression is widely used as a marker of totipotency, the role of this retrotransposon in mouse embryogenesis remains elusive. Here, we show that full-length MERVL transcripts, but not encoded retroviral proteins, are essential for accurate regulation of the host transcriptome and chromatin state during preimplantation development. Both knockdown and CRISPRi-based repression of MERVL result in embryonic lethality due to defects in differentiation and genomic stability. Furthermore, transcriptome and epigenome analysis revealed that loss of MERVL transcripts led to retention of an accessible chromatin state at, and aberrant expression of, a subset of two-cell-specific genes. Taken together, our results suggest a model in which an endogenous retrovirus plays a key role in regulating host cell fate potential.
    MeSH term(s) Mice ; Animals ; Retroelements/genetics ; Gene Expression Regulation, Developmental/genetics ; Embryonic Development/genetics ; Chromatin/genetics ; Chromatin/metabolism ; Zygote/metabolism
    Chemical Substances Retroelements ; Chromatin
    Language English
    Publishing date 2023-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/s41588-023-01324-y
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  8. Article ; Online: Piwi suppresses transcription of Brahma-dependent transposons via Maelstrom in ovarian somatic cells.

    Onishi, Ryo / Sato, Kaoru / Murano, Kensaku / Negishi, Lumi / Siomi, Haruhiko / Siomi, Mikiko C

    Science advances

    2020  Volume 6, Issue 50

    Abstract: ... ...

    Abstract Drosophila
    MeSH term(s) Animals ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Drosophila/genetics ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Female ; Gene Silencing ; Ovary ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Trans-Activators/metabolism
    Chemical Substances Argonaute Proteins ; Cell Cycle Proteins ; Drosophila Proteins ; RNA, Small Interfering ; Trans-Activators ; brm protein, Drosophila ; piwi protein, Drosophila
    Language English
    Publishing date 2020-12-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.aaz7420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: [Non-coding RNAs: where we are and where we are heading].

    Siomi, Haruhiko

    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme

    2008  Volume 53, Issue 15, Page(s) 1926–1931

    MeSH term(s) Animals ; Humans ; MicroRNAs ; RNA Interference ; RNA, Small Interfering ; RNA, Untranslated
    Chemical Substances MicroRNAs ; RNA, Small Interfering ; RNA, Untranslated
    Language Japanese
    Publishing date 2008-12
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 391163-9
    ISSN 0039-9450
    ISSN 0039-9450
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Mod(mdg4) variants repress telomeric retrotransposon HeT-A by blocking subtelomeric enhancers.

    Takeuchi, Chikara / Yokoshi, Moe / Kondo, Shu / Shibuya, Aoi / Saito, Kuniaki / Fukaya, Takashi / Siomi, Haruhiko / Iwasaki, Yuka W

    Nucleic acids research

    2022  Volume 50, Issue 20, Page(s) 11580–11599

    Abstract: Telomeres in Drosophila are composed of sequential non-LTR retrotransposons HeT-A, TART and TAHRE. Although they are repressed by the PIWI-piRNA pathway or heterochromatin in the germline, the regulation of these retrotransposons in somatic cells is ... ...

    Abstract Telomeres in Drosophila are composed of sequential non-LTR retrotransposons HeT-A, TART and TAHRE. Although they are repressed by the PIWI-piRNA pathway or heterochromatin in the germline, the regulation of these retrotransposons in somatic cells is poorly understood. In this study, we demonstrated that specific splice variants of Mod(mdg4) repress HeT-A by blocking subtelomeric enhancers in ovarian somatic cells. Among the variants, we found that the Mod(mdg4)-N variant represses HeT-A expression the most efficiently. Subtelomeric sequences bound by Mod(mdg4)-N block enhancer activity within subtelomeric TAS-R repeats. This enhancer-blocking activity is increased by the tandem association of Mod(mdg4)-N to repetitive subtelomeric sequences. In addition, the association of Mod(mdg4)-N couples with the recruitment of RNA polymerase II to the subtelomeres, which reinforces its enhancer-blocking function. Our findings provide novel insights into how telomeric retrotransposons are regulated by the specific variants of insulator proteins associated with subtelomeric sequences.
    Language English
    Publishing date 2022-11-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkac1034
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