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  1. Article ; Online: The Musashi RNA binding proteins direct the translational activation of key pituitary mRNAs.

    Banik, Jewel / Moreira, Ana Rita Silva / Lim, Juchan / Tomlinson, Sophia / Hardy, Linda L / Lagasse, Alex / Haney, Anessa / Crimmins, Meghan R / Boehm, Ulrich / Odle, Angela K / MacNicol, Melanie C / Childs, Gwen V / MacNicol, Angus M

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 5918

    Abstract: The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of a wide variety of physiological processes including reproduction, growth, metabolism and stress responses. The distinct hormone-producing cell lineages ... ...

    Abstract The pituitary functions as a master endocrine gland that secretes hormones critical for regulation of a wide variety of physiological processes including reproduction, growth, metabolism and stress responses. The distinct hormone-producing cell lineages within the pituitary display remarkable levels of cell plasticity that allow remodeling of the relative proportions of each hormone-producing cell population to meet organismal demands. The molecular mechanisms governing pituitary cell plasticity have not been fully elucidated. Our recent studies have implicated a role for the Musashi family of sequence-specific mRNA binding proteins in the control of pituitary hormone production, pituitary responses to hypothalamic stimulation and modulation of pituitary transcription factor expression in response to leptin signaling. To date, these actions of Musashi in the pituitary appear to be mediated through translational repression of the target mRNAs. Here, we report Musashi1 directs the translational activation, rather than repression, of the Prop1, Gata2 and Nr5a1 mRNAs which encode key pituitary lineage specification factors. We observe that Musashi1 further directs the translational activation of the mRNA encoding the glycolipid Neuronatin (Nnat) as determined both in mRNA reporter assays as well as in vivo. Our findings suggest a complex bifunctional role for Musashi1 in the control of pituitary cell function.
    MeSH term(s) RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA-Binding Proteins/metabolism ; Pituitary Gland/metabolism ; Protein Processing, Post-Translational ; Pituitary Hormones/metabolism
    Chemical Substances RNA, Messenger ; RNA-Binding Proteins ; Pituitary Hormones
    Language English
    Publishing date 2024-03-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-56002-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Musashi Exerts Control of Gonadotrope Target mRNA Translation During the Mouse Estrous Cycle.

    Moreira, Ana Rita Silva / Lim, Juchan / Urbaniak, Alicja / Banik, Jewel / Bronson, Katherine / Lagasse, Alex / Hardy, Linda / Haney, Anessa / Allensworth, Melody / Miles, Tiffany K / Gies, Allen / Byrum, Stephanie D / Wilczynska, Ania / Boehm, Ulrich / Kharas, Michael / Lengner, Christopher / MacNicol, Melanie C / Childs, Gwen V / MacNicol, Angus M /
    Odle, Angela K

    Endocrinology

    2023  Volume 164, Issue 9

    Abstract: The anterior pituitary controls key biological processes, including growth, metabolism, reproduction, and stress responses through distinct cell types that each secrete specific hormones. The anterior pituitary cells show a remarkable level of cell type ... ...

    Abstract The anterior pituitary controls key biological processes, including growth, metabolism, reproduction, and stress responses through distinct cell types that each secrete specific hormones. The anterior pituitary cells show a remarkable level of cell type plasticity that mediates the shifts in hormone-producing cell populations that are required to meet organismal needs. The molecular mechanisms underlying pituitary cell plasticity are not well understood. Recent work has implicated the pituitary stem cell populations and specifically, the mRNA binding proteins of the Musashi family in control of pituitary cell type identity. In this study we have identified the target mRNAs that mediate Musashi function in the adult mouse pituitary and demonstrate the requirement for Musashi function in vivo. Using Musashi RNA immunoprecipitation, we identify a cohort of 1184 mRNAs that show specific Musashi binding. Identified Musashi targets include the Gnrhr mRNA, which encodes the gonadotropin-releasing hormone receptor (GnRHR), and the Fshb mRNA, encoding follicle-stimulating hormone (FSH). Reporter assays reveal that Musashi functions to exert repression of translation of the Fshb mRNA, in addition to the previously observed repression of the Gnrhr mRNA. Importantly, mice engineered to lack Musashi in gonadotropes demonstrate a failure to repress translation of the endogenous Gnrhr and Fshb mRNAs during the estrous cycle and display a significant heterogeneity in litter sizes. The range of identified target mRNAs suggests that, in addition to these key gonadotrope proteins, Musashi may exert broad regulatory control over the pituitary proteome in a cell type-specific manner.
    MeSH term(s) Mice ; Animals ; Gonadotrophs/metabolism ; Follicle Stimulating Hormone/metabolism ; Carrier Proteins/metabolism ; Protein Biosynthesis/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
    Chemical Substances Follicle Stimulating Hormone (9002-68-0) ; Carrier Proteins ; RNA, Messenger
    Language English
    Publishing date 2023-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqad113
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Control of the Anterior Pituitary Cell Lineage Regulator POU1F1 by the Stem Cell Determinant Musashi.

    Allensworth-James, Melody / Banik, Jewel / Odle, Angela / Hardy, Linda / Lagasse, Alex / Moreira, Ana Rita Silva / Bird, Jordan / Thomas, Christian L / Avaritt, Nathan / Kharas, Michael G / Lengner, Christopher J / Byrum, Stephanie D / MacNicol, Melanie C / Childs, Gwen V / MacNicol, Angus M

    Endocrinology

    2020  Volume 162, Issue 3

    Abstract: The adipokine leptin regulates energy homeostasis through ubiquitously expressed leptin receptors. Leptin has a number of major signaling targets in the brain, including cells of the anterior pituitary (AP). We have previously reported that mice lacking ... ...

    Abstract The adipokine leptin regulates energy homeostasis through ubiquitously expressed leptin receptors. Leptin has a number of major signaling targets in the brain, including cells of the anterior pituitary (AP). We have previously reported that mice lacking leptin receptors in AP somatotropes display growth hormone (GH) deficiency, metabolic dysfunction, and adult-onset obesity. Among other targets, leptin signaling promotes increased levels of the pituitary transcription factor POU1F1, which in turn regulates the specification of somatotrope, lactotrope, and thyrotrope cell lineages within the AP. Leptin's mechanism of action on somatotropes is sex dependent, with females demonstrating posttranscriptional control of Pou1f1 messenger RNA (mRNA) translation. Here, we report that the stem cell marker and mRNA translational control protein, Musashi1, exerts repression of the Pou1f1 mRNA. In female somatotropes, Msi1 mRNA and protein levels are increased in the mouse model that lacks leptin signaling (Gh-CRE Lepr-null), coincident with lack of POU1f1 protein, despite normal levels of Pou1f1 mRNA. Single-cell RNA sequencing of pituitary cells from control female animals indicates that both Msi1 and Pou1f1 mRNAs are expressed in Gh-expressing somatotropes, and immunocytochemistry confirms that Musashi1 protein is present in the somatotrope cell population. We demonstrate that Musashi interacts directly with the Pou1f1 mRNA 3' untranslated region and exerts translational repression of a Pou1f1 mRNA translation reporter in a leptin-sensitive manner. Musashi immunoprecipitation from whole pituitary reveals coassociated Pou1f1 mRNA. These findings suggest a mechanism in which leptin stimulation is required to reverse Musashi-mediated Pou1f1 mRNA translational control to coordinate AP somatotrope function with metabolic status.
    MeSH term(s) Animals ; Cell Lineage/genetics ; Cells, Cultured ; Female ; Gene Expression Regulation, Developmental ; Mice ; Mice, 129 Strain ; Mice, Transgenic ; NIH 3T3 Cells ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/physiology ; Pituitary Gland, Anterior/cytology ; Pituitary Gland, Anterior/growth & development ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/physiology ; Somatotrophs/metabolism ; Stem Cells/cytology ; Stem Cells/metabolism ; Transcription Factor Pit-1/genetics
    Chemical Substances Msi1h protein, mouse ; Nerve Tissue Proteins ; Pit1 protein, mouse ; RNA-Binding Proteins ; Transcription Factor Pit-1
    Language English
    Publishing date 2020-12-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqaa245
    Database MEDical Literature Analysis and Retrieval System OnLINE

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