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Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by IRPs

Item Type:Article
Title:Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by IRPs
Creators Name:Sanchez, M. and Galy, B. and Schwanhaeusser, B. and Blake, J. and Baehr-Ivacevic, T. and Benes, V. and Selbach, M. and Muckenthaler, M.U. and Hentze, M.W.
Abstract:Iron regulatory proteins (IRP) 1 and 2 are RNA-binding proteins that control cellular iron metabolism by binding to conserved RNA motifs called "iron-responsive elements" (IREs). The currently known IRP-binding mRNAs encode proteins involved in iron uptake, storage and release as well as e.g. heme synthesis. To systematically define the IRE/IRP regulatory network on a transcriptome-wide scale, IRP1/IRE and IRP2/IRE mRNP complexes were immunoselected and the mRNA composition was determined using microarrays. We identify 35 novel mRNAs that bind both IRP1 and IRP2, and also report for the first time cellular mRNAs with exclusive specificity for IRP-1 or -2. To further explore cellular iron metabolism at a system-wide level, we undertook proteomic analysis by pulsed SILAC in an iron-modulated mouse hepatic cell line and in bone marrow derived macrophages from IRP1- and IRP2-deficient mice. This work investigates cellular iron metabolism in unprecedented depth and defines a wide network of mRNAs and proteins with iron- and/or IRP-dependent regulation.
Keywords:Gene Expression Profiling, Gene Expression Regulation, Inbred C57BL Mice, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Iron-Regulatory Proteins, Knockout Mice, Liver, Macrophages, Proteome, Messenger RNA, Microarray Analysis, RNA-Binding Proteins, Transcriptome, Tumor Cell Line, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:118
Number:22
Page Range:e168-e179
Date:24 November 2011
Official Publication:https://doi.org/10.1182/blood-2011-04-343541
PubMed:View item in PubMed

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