IRON REGULATORY PROTEIN PREVENTS BINDING OF THE 43S TRANSLATION PRE-INITIATION COMPLEX TO FERRITIN AND EALAS MESSENGER-RNAS

被引:226
作者
GRAY, NK [1 ]
HENTZE, MW [1 ]
机构
[1] EUROPEAN MOLEC BIOL LAB,GENE EXPRESS PROGRAMME,D-69117 HEIDELBERG,GERMANY
关键词
EALAS; IRON-RESPONSIVE ELEMENTS; POSTTRANSCRIPTIONAL REGULATION; RNA-PROTEIN INTERACTIONS; RIBOSOME BINDING;
D O I
10.1002/j.1460-2075.1994.tb06699.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
Translation of ferritin and erythroid 5-aminolevulinate synthase (eALAS) mRNAs is regulated by iron via mRNA-protein interactions between iron-responsive elements (IREs) and iron regulatory protein (IRP). In iron-depleted cells, IRP binds to single IREs located in the 5' untranslated regions of ferritin and eALAS mRNAs and represses translation initiation. The molecular mechanism underlying this translational repression was investigated using reconstituted, IRE-IRP-regulated, cell-free translation systems. The IRE-IRP interaction is shown to prevent the association of the 43S translation pre-initiation complex (including the small ribosomal subunit) with the mRNA. Studies with the spliceosomal protein U1A and mRNAs which harbour specific binding sites for this protein in place of an IRE furthermore reveal that the 5' termini of mRNAs are generally sensitive to repressor protein-mediated inhibition of 43S pre-initiation complex binding.
引用
收藏
页码:3882 / 3891
页数:10
相关论文
共 49 条
[1]  
ANTHONY DD, 1992, J BIOL CHEM, V267, P1554
[2]   BOTH SUBUNITS OF RAT-LIVER FERRITIN ARE REGULATED AT A TRANSLATIONAL LEVEL BY IRON INDUCTION [J].
AZIZ, N ;
MUNRO, HN .
NUCLEIC ACIDS RESEARCH, 1986, 14 (02) :915-927
[3]   IRON REGULATES FERRITIN MESSENGER-RNA TRANSLATION THROUGH A SEGMENT OF ITS 5' UNTRANSLATED REGION [J].
AZIZ, N ;
MUNRO, HN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8478-8482
[4]   IRON-RESPONSIVE ELEMENTS - REGULATORY RNA SEQUENCES THAT CONTROL MESSENGER-RNA LEVELS AND TRANSLATION [J].
CASEY, JL ;
HENTZE, MW ;
KOELLER, DM ;
CAUGHMAN, SW ;
ROUAULT, TA ;
KLAUSNER, RD ;
HARFORD, JB .
SCIENCE, 1988, 240 (4854) :924-928
[5]   IDENTIFICATION OF AN RNA-BINDING SITE FOR HUMAN THYMIDYLATE SYNTHASE [J].
CHU, E ;
VOELLER, D ;
KOELLER, DM ;
DRAKE, JC ;
TAKIMOTO, CH ;
MALEY, GF ;
MALEY, F ;
ALLEGRA, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (02) :517-521
[6]   MODULATION OF THE RNA-BINDING ACTIVITY OF A REGULATORY PROTEIN BY IRON INVITRO - SWITCHING BETWEEN ENZYMATIC AND GENETIC FUNCTION [J].
CONSTABLE, A ;
QUICK, S ;
GRAY, NK ;
HENTZE, MW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (10) :4554-4558
[7]   HUMAN ERYTHROID 5-AMINOLEVULINATE SYNTHASE - PROMOTER ANALYSIS AND IDENTIFICATION OF AN IRON-RESPONSIVE ELEMENT IN THE MESSENGER-RNA [J].
COX, TC ;
BAWDEN, MJ ;
MARTIN, A ;
MAY, BK .
EMBO JOURNAL, 1991, 10 (07) :1891-1902
[8]  
DABEVA MD, 1993, J BIOL CHEM, V268, P19669
[9]   IDENTIFICATION OF A NOVEL IRON-RESPONSIVE ELEMENT IN MURINE AND HUMAN ERYTHROID DELTA-AMINOLEVULINIC-ACID SYNTHASE MESSENGER-RNA [J].
DANDEKAR, T ;
STRIPECKE, R ;
GRAY, NK ;
GOOSSEN, B ;
CONSTABLE, A ;
JOHANSSON, HE ;
HENTZE, MW .
EMBO JOURNAL, 1991, 10 (07) :1903-1909
[10]   BIOSYNTHESIS OF NITRIC-OXIDE ACTIVATES IRON REGULATORY FACTOR IN MACROPHAGES [J].
DRAPIER, JC ;
HIRLING, H ;
WIETZERBIN, J ;
KALDY, P ;
KUHN, LC .
EMBO JOURNAL, 1993, 12 (09) :3643-3649