Diurnal control of iron responsive element containing mRNAs through iron regulatory proteins IRP1 and IRP2 is mediated by feeding rhythms.

Autor: Nadimpalli HP; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Katsioudi G; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Arpa ES; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Chikhaoui L; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Arpat AB; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Liechti A; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland., Palais G; German Cancer Research Center (DKFZ), Division of Virus-Associated Carcinogenesis, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany., Tessmer C; German Cancer Research Center (DKFZ), Core Facility Antibodies, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany., Hofmann I; German Cancer Research Center (DKFZ), Core Facility Antibodies, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany., Galy B; German Cancer Research Center (DKFZ), Division of Virus-Associated Carcinogenesis, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany., Gatfield D; Center for Integrative Genomics, University of Lausanne, Lausanne, 1015, Switzerland. david.gatfield@unil.ch.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2024 May 21; Vol. 25 (1), pp. 128. Date of Electronic Publication: 2024 May 21.
DOI: 10.1186/s13059-024-03270-2
Abstrakt: Background: 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.
Results: 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.
Conclusions: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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