Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins
Author
Sanchez, Mayka
Galy, Bruno
Schwanhaeusser, Bjoern
Blake, Jonathon
Bähr-Ivacevic, Tomi
Benes, Vladimir
Selbach, Matthias
Muckenthaler, Martina U.
Hentze, Matthias W.
Publication date
2011ISSN
0006-4971
Abstract
Iron regulatory proteins (IRPs) 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 heme synthesis. To systematically define the IRE/IRP regulatory network on a transcriptome-wide scale, IRP1/IRE and IRP2/IRE messenger ribonucleoprotein complexes were immunoselected, and the mRNA composition was determined using microarrays. We identify 35 novel mRNAs that bind both IRP1 and IRP2, and we also report for the first time cellular mRNAs with exclusive specificity for IRP1 or IRP2. To further explore cellular iron metabolism at a system-wide level, we undertook proteomic analysis by pulsed stable isotope labeling by amino acids in cell culture 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-dependent regulation, IRP-dependent regulation, or both.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Ferro
Proteïna reguladora
RNA
Missatger
Ratolins
Proteoma
Llocs d'entrada de ribosomes interns
Hierro
Proteína reguladora
ARN
Mensajero
Ratones
Proteoma
Sitios internos de entrada de ribosomas
Iron
Regulatory protein
RNA
Messenger
Mice
Proteome
Internal ribosome entry sites
Pages
12
Publisher
ASH Publications
Collection
168;179
Is part of
Blood
Citation
Sanchez, Mayka; Galy, Bruno; Schwanhaeusser, Bjoern [et al.]. Iron regulatory protein-1 and -2: transcriptome-wide definition of binding mRNAs and shaping of the cellular proteome by iron regulatory proteins. Blood, 2011, 118 (22), e168–e179. Disponible en: <https://ashpublications.org/blood/article/118/22/e168/29216/Iron-regulatory-protein-1-and-2-transcriptome-wide>. Fecha de acceso: 22 ene. 2024. DOI: 10.1182/blood-2011-04-343541
This item appears in the following Collection(s)
- Ciències de la Salut [725]
Rights
© 2011 American Society of Hematology