Control of Systemic Iron Homeostasis by the 3’ Iron-Responsive Element of Divalent Metal Transporter 1 in Mice

Autor: Michael Bonadonna, Ferran Celma Nos, Gael Palais, Tomasa Barrientos, Elisabeth Tybl, Sanjay Gupta, Zoubida Karim, Nancy C. Andrews, Mayka Sanchez, Bruno Galy, Hiromi Gunshin
Přispěvatelé: Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Untranslated region
Letter
[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
03 medical and health sciences
0302 clinical medicine
Iron homeostasis
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Dietary iron
Messenger RNA
biology
lcsh:RC633-647.5
Chemistry
fungi
digestive
oral
and skin physiology
Transporter
Assimilation (biology)
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
lcsh:Diseases of the blood and blood-forming organs
Hematology
DMT1
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Divalent metal
Cell biology
Biochemistry
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
biology.protein
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
030217 neurology & neurosurgery
Zdroj: HemaSphere
HemaSphere, Lippincott, Williams & Wilkins, 2020, 4 (5), pp.e459. ⟨10.1097/HS9.0000000000000459⟩
HemaSphere, Vol 4, Iss 5, p e459 (2020)
ISSN: 2572-9241
Popis: Divalent metal transporter 1 (DMT1) is essential for dietary iron assimilation and erythroid iron acquisition. The 3’ untranslated region of the murine DMT1 mRNA contains an iron responsive element (IRE) that is conserved in humans but whose functional role remains unclear. We generated and analyzed mice with targeted disruption of the DMT1 3’IRE. These animals display hypoferremia during the suckling period, associated with a reduction of DMT1 mRNA and protein in the intestine. In contrast, adult mice exhibit hyperferremia, accompanied by enlargement of hepatic and splenic iron stores. Intriguingly, disruption of the DMT1 3’IRE in adult animals augments intestinal DMT1 expression, in part due to increased mRNA translation. Hence, during postnatal growth, the DMT1 3’IRE promotes intestinal DMT1 expression and secures iron sufficiency; in adulthood, it suppresses DMT1 and prevents systemic iron loading. This work demonstrates that the 3’IRE of DMT1 plays a role in the control of DMT1 expression and systemic iron homeostasis, and reveals an age-dependent switch in its activity.Key pointsTargeted mutagenesis of the 3’IRE of DMT1 in mice reveals its importance for maintenance of systemic iron homeostasis.The 3’IRE stimulates intestinal DMT1 expression and prevents hypoferremia during early life, but exerts opposite effects in adulthood
Databáze: OpenAIRE
Externí odkaz: