Počet záznamů: 1  

Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification

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    0539719 - ÚMG 2021 RIV GB eng J - Článek v odborném periodiku
    dos Santos, M.C.F. - Anderson, C.P. - Rozman, Jan … celkem 17 autorů
    Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification.
    Nature Communications. Roč. 11, č. 1 (2020), č. článku 296. E-ISSN 2041-1723
    Institucionální podpora: RVO:68378050
    Klíčová slova: genome-wide association * beta-cell failure * endoplasmic-reticulum * responsive element * deficiency anemia * cdkal1 * homeostasis * proteins * biogenesis * secretion
    Obor OECD: Developmental biology
    Impakt faktor: 14.919, rok: 2020
    Způsob publikování: Open access
    https://www.nature.com/articles/s41467-019-14004-5

    Regulation of cellular iron homeostasis is crucial as both iron excess and deficiency cause hematological and neurodegenerative diseases. Here we show that mice lacking iron-regulatory protein 2 (Irp2), a regulator of cellular iron homeostasis, develop diabetes. Irp2 post-transcriptionally regulates the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-storage protein ferritin, and dysregulation of these proteins due to Irp2 loss causes functional iron deficiency in beta cells. This impairs Fe-S cluster biosynthesis, reducing the function of Cdkal1, an Fe-S cluster enzyme that catalyzes methylthiolation of t(6)A37 in tRNA(UUU)(Lys) to ms(2)t(6)A37. As a consequence, lysine codons in proinsulin are misread and proinsulin processing is impaired, reducing insulin content and secretion. Iron normalizes ms(2)t(6)A37 and proinsulin lysine incorporation, restoring insulin content and secretion in Irp2(-/-) beta cells. These studies reveal a previously unidentified link between insulin processing and cellular iron deficiency that may have relevance to type 2 diabetes in humans.
    Trvalý link: http://hdl.handle.net/11104/0317424

     
     
Počet záznamů: 1  

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