Iron regulatory proteins 1 and 2 bind distinct sets of RNA target sequences.

Details

Serval ID
serval:BIB_4536
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Iron regulatory proteins 1 and 2 bind distinct sets of RNA target sequences.
Journal
Journal of Biological Chemistry
Author(s)
Henderson B.R., Menotti E., Kühn L.C.
ISSN
0021-9258
Publication state
Published
Issued date
1996
Volume
271
Number
9
Pages
4900-4908
Language
english
Abstract
Iron regulatory proteins (IRPs) 1 and 2 bind with equally high affinity to iron-responsive element (IRE) RNA stem-loops located in mRNA untranslated regions and, thereby, post-transcriptionally regulate several genes of iron metabolism. In this study we define the RNA-binding specificities of mouse IRP-1 and IRP-2. By screening loop mutations of the ferritin H-chain IRE, we show that both IRPs bind well to a large number of IRE-like sequences. More significantly, each IRP was found to recognize a unique subset of IRE-like targets. These IRP-specific groups of IREs are distinct from one another and are characterized by changes in certain paired (IRP-1) or unpaired (IRP-2) loop nucleotides. We further demonstrate the application of such sequences as unique probes to detect and distinguish IRP-1 from IRP-2 in human cells, and observe that the IRPs are regulated similarly by iron and reducing agents in human and rodent cells. Importantly, the ability of each IRP to recognize an exclusive subset of IREs was conserved between species. These findings suggest that IRP-1 and IRP-2 may each regulate unique mRNA targets in vivo, possibly extending their function beyond the regulation of intracellular iron homeostasis.
Keywords
Animals, Base Sequence, Binding Sites, Cell Line, Cycloheximide/pharmacology, Deferoxamine/pharmacology, HL-60 Cells, Hela Cells, Humans, Iron/pharmacology, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Iron-Regulatory Proteins, Melanoma, Experimental, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Protein Structure, Secondary, RNA Probes, RNA Processing, Post-Transcriptional, RNA, Messenger/chemistry, RNA, Messenger/metabolism, RNA-Binding Proteins/chemistry, RNA-Binding Proteins/metabolism, Substrate Specificity, Tumor Cells, Cultured
Pubmed
Create date
19/11/2007 12:40
Last modification date
20/08/2019 13:49
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