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  1. Artikel ; Online: ADARs regulate cuticle collagen expression and promote survival to pathogen infection.

    Dhakal, Alfa / Salim, Chinnu / Skelly, Mary / Amichan, Yarden / Lamm, Ayelet T / Hundley, Heather A

    BMC biology

    2024  Band 22, Heft 1, Seite(n) 37

    Abstract: Background: In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that ... ...

    Abstract Background: In all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA-binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking.
    Results: Here, by analyzing adr-1 and adr-2 null mutants in well-established slow-killing assays, we find that both Caenorhabditis elegans ADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans. Furthermore, our high-throughput sequencing and genetic analysis reveal that ADR-1 and ADR-2 function in the same pathway to regulate collagen expression. Consistent with this finding, our scanning electron microscopy studies indicate adr-1;adr-2 mutant animals also have altered cuticle morphology prior to pathogen exposure.
    Conclusions: Our data uncover a critical role of the C. elegans ADAR family of RNA-binding proteins in promoting cuticular collagen expression, which represents a new post-transcriptional regulatory node that influences the extracellular matrix. In addition, we provide the first evidence that ADAR mutant animals have altered susceptibility to infection with several opportunistic human pathogens, suggesting a broader role of ADARs in altering physical barriers to infection to influence innate immunity.
    Mesh-Begriff(e) Animals ; Humans ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; RNA Editing ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Collagen/genetics ; Collagen/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
    Chemische Substanzen Caenorhabditis elegans Proteins ; Adenosine Deaminase (EC 3.5.4.4) ; Collagen (9007-34-5) ; RNA-Binding Proteins
    Sprache Englisch
    Erscheinungsdatum 2024-02-16
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2133020-7
    ISSN 1741-7007 ; 1741-7007
    ISSN (online) 1741-7007
    ISSN 1741-7007
    DOI 10.1186/s12915-024-01840-1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: ADARs employ a neural-specific mechanism to regulate PQM-1 expression and survival from hypoxia.

    Mahapatra, Ananya / Dhakal, Alfa / Noguchi, Aika / Vadlamani, Pranathi / Hundley, Heather A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about ... ...

    Abstract The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal's surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues. The transcription factor PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as impacting survival from hypoxia. Herein, we reveal a novel mechanism for regulating PQM-1 expression specifically in neural cells of larval animals. Our studies reveal that the RNA binding protein, ADR-1, binds to
    Sprache Englisch
    Erscheinungsdatum 2023-05-05
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.05.05.539519
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: ADAR-mediated regulation of PQM-1 expression in neurons impacts gene expression throughout C. elegans and regulates survival from hypoxia.

    Mahapatra, Ananya / Dhakal, Alfa / Noguchi, Aika / Vadlamani, Pranathi / Hundley, Heather A

    PLoS biology

    2023  Band 21, Heft 9, Seite(n) e3002150

    Abstract: The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about ... ...

    Abstract The ability to alter gene expression programs in response to changes in environmental conditions is central to the ability of an organism to thrive. For most organisms, the nervous system serves as the master regulator in communicating information about the animal's surroundings to other tissues. The information relay centers on signaling pathways that cue transcription factors in a given cell type to execute a specific gene expression program, but also provide a means to signal between tissues. The transcription factor PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as impacting survival from hypoxia. Herein, we reveal a novel mechanism for regulating PQM-1 expression specifically in neural cells of larval animals. Our studies reveal that the RNA-binding protein (RBP), ADR-1, binds to pqm-1 mRNA in neural cells. This binding is regulated by the presence of a second RBP, ADR-2, which when absent leads to reduced expression of both pqm-1 and downstream PQM-1 activated genes. Interestingly, we find that neural pqm-1 expression is sufficient to impact gene expression throughout the animal and affect survival from hypoxia, phenotypes that we also observe in adr mutant animals. Together, these studies reveal an important posttranscriptional gene regulatory mechanism in Caenorhabditis elegans that allows the nervous system to sense and respond to environmental conditions to promote organismal survival from hypoxia.
    Mesh-Begriff(e) Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Hypoxia/genetics ; Hypoxia/metabolism ; Neurons/metabolism ; Gene Expression ; Longevity/genetics ; Gene Expression Regulation ; Trans-Activators/metabolism
    Chemische Substanzen Caenorhabditis elegans Proteins ; PQM-1 protein, C elegans ; Trans-Activators
    Sprache Englisch
    Erscheinungsdatum 2023-09-25
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002150
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6193: Hefte anzeigen Standort:
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  4. Artikel ; Online: Profiling neural editomes reveals a molecular mechanism to regulate RNA editing during development.

    Rajendren, Suba / Dhakal, Alfa / Vadlamani, Pranathi / Townsend, Jack / Deffit, Sarah N / Hundley, Heather A

    Genome research

    2020  Band 31, Heft 1, Seite(n) 27–39

    Abstract: Adenosine (A) to inosine (I) RNA editing contributes to transcript diversity and modulates gene expression in a dynamic, cell type-specific manner. During mammalian brain development, editing of specific adenosines increases, whereas the expression of A- ... ...

    Abstract Adenosine (A) to inosine (I) RNA editing contributes to transcript diversity and modulates gene expression in a dynamic, cell type-specific manner. During mammalian brain development, editing of specific adenosines increases, whereas the expression of A-to-I editing enzymes remains unchanged, suggesting molecular mechanisms that mediate spatiotemporal regulation of RNA editing exist. Herein, by using a combination of biochemical and genomic approaches, we uncover a molecular mechanism that regulates RNA editing in a neural- and development-specific manner. Comparing editomes during development led to the identification of neural transcripts that were edited only in one life stage. The stage-specific editing is largely regulated by differential gene expression during neural development. Proper expression of nearly one-third of the neurodevelopmentally regulated genes is dependent on
    Mesh-Begriff(e) Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Inosine/genetics ; Inosine/metabolism ; RNA Editing
    Chemische Substanzen Caenorhabditis elegans Proteins ; Inosine (5A614L51CT) ; Adenosine Deaminase (EC 3.5.4.4) ; Adr-1 protein, C elegans (EC 3.5.4.4) ; Adr-2 protein, C elegans (EC 3.5.4.4) ; Adenosine (K72T3FS567)
    Sprache Englisch
    Erscheinungsdatum 2020-12-18
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.267575.120
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 3729: Hefte anzeigen Standort:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MG 8: Hefte anzeigen

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