Titre
Diurnal control of iron responsive element containing mRNAs through iron regulatory proteins IRP1 and IRP2 is mediated by feeding rhythms.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Nadimpalli, H.P.
Auteure/Auteur
Katsioudi, G.
Auteure/Auteur
Arpa, E.S.
Auteure/Auteur
Chikhaoui, L.
Auteure/Auteur
Arpat, A.B.
Auteure/Auteur
Liechti, A.
Auteure/Auteur
Palais, G.
Auteure/Auteur
Tessmer, C.
Auteure/Auteur
Hofmann, I.
Auteure/Auteur
Galy, B.
Auteure/Auteur
Gatfield, D.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1474-760X
Statut éditorial
Publié
Date de publication
2024-05-21
Volume
25
Numéro
1
Première page
128
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Cellular iron homeostasis is regulated by iron regulatory proteins (IRP1 and IRP2) that sense iron levels (and other metabolic cues) and modulate mRNA translation or stability via interaction with iron regulatory elements (IREs). IRP2 is viewed as the primary regulator in the liver, yet our previous datasets showing diurnal rhythms for certain IRE-containing mRNAs suggest a nuanced temporal control mechanism. The purpose of this study is to gain insights into the daily regulatory dynamics across IRE-bearing mRNAs, specific IRP involvement, and underlying systemic and cellular rhythmicity cues in mouse liver.
We uncover high-amplitude diurnal oscillations in the regulation of key IRE-containing transcripts in the liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this timepoint still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic.
Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
We uncover high-amplitude diurnal oscillations in the regulation of key IRE-containing transcripts in the liver, compatible with maximal IRP activity at the onset of the dark phase. Although IRP2 protein levels also exhibit some diurnal variations and peak at the light-dark transition, ribosome profiling in IRP2-deficient mice reveals that maximal repression of target mRNAs at this timepoint still occurs. We further find that diurnal regulation of IRE-containing mRNAs can continue in the absence of a functional circadian clock as long as feeding is rhythmic.
Our findings suggest temporally controlled redundancy in IRP activities, with IRP2 mediating regulation of IRE-containing transcripts in the light phase and redundancy, conceivably with IRP1, at dark onset. Moreover, we highlight the significance of feeding-associated signals in driving rhythmicity. Our work highlights the dynamic nature and regulatory complexity in a metabolic pathway that had previously been considered well-understood.
Sujets
PID Serval
serval:BIB_D0D944AB65AF
PMID
Open Access
Oui
Date de création
2024-05-24T07:41:06.651Z
Date de création dans IRIS
2025-05-21T00:23:03Z
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Nom
38773499_BIB_D0D944AB65AF.pdf
Version du manuscrit
preprint
Licence
https://creativecommons.org/licenses/by/4.0
Taille
7.18 MB
Format
Adobe PDF
PID Serval
serval:BIB_D0D944AB65AF.P001
URN
urn:nbn:ch:serval-BIB_D0D944AB65AF0
Somme de contrôle
(MD5):cd0c98c91a080dffa7ba44109a5c06ee