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  1. Article: The role of RNA-binding proteins in orchestrating germline development in

    Albarqi, Mennatallah M Y / Ryder, Sean P

    Frontiers in cell and developmental biology

    2023  Volume 10, Page(s) 1094295

    Abstract: RNA passed from parents to progeny controls several aspects of early development. The germline of the free-living ... ...

    Abstract RNA passed from parents to progeny controls several aspects of early development. The germline of the free-living nematode
    Language English
    Publishing date 2023-01-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.1094295
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The endogenous mex-3 3´UTR is required for germline repression and contributes to optimal fecundity in C. elegans.

    Albarqi, Mennatallah M Y / Ryder, Sean P

    PLoS genetics

    2021  Volume 17, Issue 8, Page(s) e1009775

    Abstract: RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of ... ...

    Abstract RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of parental transcripts to control cell fate specification events prior to zygotic gene activation. The KH-domain RBP MEX-3 is conserved from nematode to human. It was first discovered in Caenorhabditis elegans, where it is essential for anterior cell fate and embryo viability. Here, we show that loss of the endogenous mex-3 3´UTR disrupts its germline expression pattern. An allelic series of 3´UTR deletion variants identify repressing regions of the UTR and demonstrate that repression is not precisely coupled to reproductive success. We also show that several RBPs regulate mex-3 mRNA through its 3´UTR to define its unique germline spatiotemporal expression pattern. Additionally, we find that both poly(A) tail length control and the translation initiation factor IFE-3 contribute to its expression pattern. Together, our results establish the importance of the mex-3 3´UTR to reproductive health and its expression in the germline. Our results suggest that additional mechanisms control MEX-3 function when 3´UTR regulation is compromised.
    MeSH term(s) 3' Untranslated Regions/genetics ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Embryonic Development/genetics ; Fertility/genetics ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/metabolism ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
    Chemical Substances 3' Untranslated Regions ; Caenorhabditis elegans Proteins ; MEX-3 protein, C elegans ; RNA, Messenger ; RNA-Binding Proteins
    Language English
    Publishing date 2021-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Regulation of Life Cycle Checkpoints and Developmental Activation of Infective Larvae in Strongyloides stercoralis by Dafachronic Acid.

    Albarqi, Mennatallah M Y / Stoltzfus, Jonathan D / Pilgrim, Adeiye A / Nolan, Thomas J / Wang, Zhu / Kliewer, Steven A / Mangelsdorf, David J / Lok, James B

    PLoS pathogens

    2016  Volume 12, Issue 1, Page(s) e1005358

    Abstract: The complex life cycle of the parasitic nematode Strongyloides stercoralis leads to either developmental arrest of infectious third-stage larvae (iL3) or growth to reproductive adults. In the free-living nematode Caenorhabditis elegans, analogous ... ...

    Abstract The complex life cycle of the parasitic nematode Strongyloides stercoralis leads to either developmental arrest of infectious third-stage larvae (iL3) or growth to reproductive adults. In the free-living nematode Caenorhabditis elegans, analogous determination between dauer arrest and reproductive growth is governed by dafachronic acids (DAs), a class of steroid hormones that are ligands for the nuclear hormone receptor DAF-12. Biosynthesis of DAs requires the cytochrome P450 (CYP) DAF-9. We tested the hypothesis that DAs also regulate S. stercoralis development via DAF-12 signaling at three points. First, we found that 1 μM Δ7-DA stimulated 100% of post-parasitic first-stage larvae (L1s) to develop to free-living adults instead of iL3 at 37°C, while 69.4±12.0% (SD) of post-parasitic L1s developed to iL3 in controls. Second, we found that 1 μM Δ7-DA prevented post-free-living iL3 arrest and stimulated 85.2±16.9% of larvae to develop to free-living rhabditiform third- and fourth-stages, compared to 0% in the control. This induction required 24-48 hours of Δ7-DA exposure. Third, we found that the CYP inhibitor ketoconazole prevented iL3 feeding in host-like conditions, with only 5.6±2.9% of iL3 feeding in 40 μM ketoconazole, compared to 98.8±0.4% in the positive control. This inhibition was partially rescued by Δ7-DA, with 71.2±16.4% of iL3 feeding in 400 nM Δ7-DA and 35 μM ketoconazole, providing the first evidence of endogenous DA production in S. stercoralis. We then characterized the 26 CYP-encoding genes in S. stercoralis and identified a homolog with sequence and developmental regulation similar to DAF-9. Overall, these data demonstrate that DAF-12 signaling regulates S. stercoralis development, showing that in the post-parasitic generation, loss of DAF-12 signaling favors iL3 arrest, while increased DAF-12 signaling favors reproductive development; that in the post-free-living generation, absence of DAF-12 signaling is crucial for iL3 arrest; and that endogenous DA production regulates iL3 activation.
    MeSH term(s) Amino Acid Sequence ; Animals ; Cholestenes/metabolism ; Disease Models, Animal ; Dogs ; Gene Expression Regulation, Developmental/physiology ; Genes, Helminth ; Gerbillinae ; Helminth Proteins/genetics ; Helminth Proteins/metabolism ; Larva/metabolism ; Life Cycle Stages ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Strongyloides stercoralis/genetics ; Strongyloides stercoralis/growth & development ; Strongyloides stercoralis/metabolism ; Strongyloidiasis/metabolism
    Chemical Substances Cholestenes ; Helminth Proteins ; Receptors, Cytoplasmic and Nuclear ; dafachronic acid
    Language English
    Publishing date 2016-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1005358
    Database MEDical Literature Analysis and Retrieval System OnLINE

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