TRANSLATIONAL REGULATION VIA IRON-RESPONSIVE ELEMENTS BY THE NITRIC-OXIDE NO-SYNTHASE PATHWAY

被引:351
作者
WEISS, G
GOOSSEN, B
DOPPLER, W
FUCHS, D
PANTOPOULOS, K
WERNERFELMAYER, G
WACHTER, H
HENTZE, MW
机构
[1] EUROPEAN MOLEC BIOL LAB, GENE EXPRESS PROGRAMME, MEYERHOFSTR 1, D-69117 HEIDELBERG, GERMANY
[2] UNIV INNSBRUCK, DEPT INTERNAL MED, A-6020 INNSBRUCK, AUSTRIA
[3] UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA
关键词
ACONITASE; ANEMIA; IRON SULFUR PROTEINS; POSTTRANSCRIPTIONAL REGULATION; RNA-PROTEIN INTERACTIONS;
D O I
10.1002/j.1460-2075.1993.tb06039.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nitric oxide (NO) produced from L-arginine by NO synthases (NOS) is a transmitter known to be involved in diverse biological processes, including immunomodulation, neurotransmission and blood vessel dilatation. We describe a novel rote of NO as a signaling molecule in post-transcriptional gene regulation. We demonstrate that induction of NOS in macrophage and non-macrophage cell lines activates RNA binding by iron regulatory factor (IRFs), the central trans regulator of mRNAs involved in cellular iron metabolism. NO-induced binding of IRF to iron-responsive elements (IRE) specifically represses the translation of transfected IRE-containing indicator mRNAs as well as the biosynthesis of the cellular iron storage protein ferritin. These findings define a new biological function of NO and identify a regulatory connection between the NO/NOS pathway and cellular iron metabolism.
引用
收藏
页码:3651 / 3657
页数:7
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