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PMID: 1903535 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Ferritin mRNA: interactions of iron regulatory element with translational regulator protein P-90 and the effect on base-paired flanking regions.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 10 ·1991-05-15 ·Pages 4166-70

Harrell CM, McKenzie AR, Patino MM, Walden WE, Theil EC

Abstract

The ferritin iron regulatory element (IRE), a conserved sequence of 28 nucleotides in a hairpin loop, is a conserved mRNA-specific translational regulatory element; flanking the IRE are regions of varying sequence, which form 9-17 base pairs close to the 5' cap. P-90 is a ferritin mRNA-specific translation regulatory protein purified from animal liver and reticulocytes. To study the P-90-RNA interaction, protein nucleases (RNase S1 and T1) and chemical nucleases FeEDTA and/or 1,10-phenanthroline-Cu were used as probes of an oligonucleotide (n = 55), containing the IRE and flanking regions (FL), and natural ferritin mRNA. Footprints and "toeprints" showed that P-90 binding was confined to the stem and loop of the IRE itself. However, P-90 altered the structure of the flanking region by increasing base stacking or helicity (RNase V1 sensitivity). Comparison of the reactivity of the IRE and flanking regions in natural mRNA and the 55-mer showed that long-range interactions included protecting bulges, single-stranded, and stacked regions from protein nucleases as well as stabilizing the P-90-RNA interaction. Structural integration of the IRE with the base-paired flanking regions was indicated by common features of reactivity (periodic hypersensitivity to FeEDTA) and changes in the FL region caused by P-90. The increased secondary structure of the IRE flanking regions caused by P-90 binding to the IRE provides a likely mechanism for blocking initiation of ferritin mRNA translation, since the combined structure (IRE + FL) is so close (8-17 nucleotides) to the cap.

MeSH Terms
Animals Base Composition Base Sequence Binding Sites Edetic Acid Ferric Compounds Ferritins/genetics Gene Expression Regulation Iron/metabolism Molecular Sequence Data Phenanthrolines Protein Biosynthesis Proteins/metabolism RNA, Messenger/genetics,metabolism Rabbits Regulatory Sequences, Nucleic Acid Ribonuclease T1/metabolism Ribonucleases/metabolism
Chemicals
Ferric Compounds Phenanthrolines Proteins RNA, Messenger Ferritins Edetic Acid Iron Ribonucleases Ribonuclease T1 ribonuclease S Fe(III)-EDTA 1,10-phenanthroline
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Harrell C M
Department of Biochemistry, North Carolina State University, Raleigh 27695-7622.
McKenzie A R
Patino M M
Walden W E
Theil E C
References (53)
53 references, click to expand
  1. Visualizing the higher order folding of a catalytic RNA molecule.
    Science. 1991 Jan 25;251(4992):401-7 PMID: 1989074
  2. Iron induction of ferritin synthesis in soybean cell suspensions.
    Plant Physiol. 1989 Jun;90(2):586-90 PMID: 16666812
  3. Trans-activation by HIV-1 Tat via a heterologous RNA binding protein.
    Cell. 1990 Aug 24;62(4):769-76 PMID: 2117500
  4. Regulation of ferritin and transferrin receptor mRNAs.
    J Biol Chem. 1990 Mar 25;265(9):4771-4 PMID: 2156853
  5. The mRNA-binding protein which controls ferritin and transferrin receptor expression is conserved during evolution.
    Nucleic Acids Res. 1990 Mar 11;18(5):1175-9 PMID: 2157191
  6. Mode of interaction of the zinc finger protein TFIIIA with a 5S RNA gene of Xenopus.
    Proc Natl Acad Sci U S A. 1990 Jul;87(14):5528-32 PMID: 2164687
  7. Cloning of the cDNA encoding an RNA regulatory protein--the human iron-responsive element-binding protein.
    Proc Natl Acad Sci U S A. 1990 Oct;87(20):7958-62 PMID: 2172968
  8. Fragments of the HIV-1 Tat protein specifically bind TAR RNA.
    Science. 1990 Sep 14;249(4974):1281-5 PMID: 2205002
  9. Evidence for conservation of ferritin sequences among plants and animals and for a transit peptide in soybean.
    J Biol Chem. 1990 Oct 25;265(30):18339-44 PMID: 2211706
  10. Derepression of ferritin messenger RNA translation by hemin in vitro.
    Science. 1990 Jan 5;247(4938):74-7 PMID: 2294594
  11. Structural requirements of iron-responsive elements for binding of the protein involved in both transferrin receptor and ferritin mRNA post-transcriptional regulation.
    Nucleic Acids Res. 1990 Apr 11;18(7):1819-24 PMID: 2336358
  12. Autogenous translational operator recognized by bacteriophage T4 DNA polymerase.
    J Mol Biol. 1990 Jun 20;213(4):749-61 PMID: 2359122
  13. The inhibition of the iron responsive element RNA-protein interaction by heme does not mimic in vivo iron regulation.
    J Biol Chem. 1990 Aug 5;265(22):12786-9 PMID: 2376574
  14. Structure of the 5' untranslated regulatory region of ferritin mRNA studied in solution.
    Nucleic Acids Res. 1990 Aug 11;18(15):4463-8 PMID: 2388828
  15. On the recognition of helical RNA by cobra venom V1 nuclease.
    J Biol Chem. 1986 Apr 25;261(12):5396-403 PMID: 2420800
  16. S4-alpha mRNA translation regulation complex. II. Secondary structures of the RNA regulatory site in the presence and absence of S4.
    J Mol Biol. 1987 Jul 20;196(2):323-32 PMID: 2443720
  17. The importance of the 3'-untranslated region in the translational control of ferritin mRNA.
    J Biol Chem. 1988 Mar 5;263(7):3071-4 PMID: 2449437
  18. Iron-responsive elements: regulatory RNA sequences that control mRNA levels and translation.
    Science. 1988 May 13;240(4854):924-8 PMID: 2452485
  19. Novel mechanism for translational control in regulation of ferritin synthesis by iron.
    Proc Natl Acad Sci U S A. 1976 Mar;73(3):857-61 PMID: 1083028
  20. Predicting optimal and suboptimal secondary structure for RNA.
    Methods Enzymol. 1990;183:281-306 PMID: 1690335
  21. Chemical nucleases: new reagents in molecular biology.
    Annu Rev Biochem. 1990;59:207-36 PMID: 1695832
  22. Translational repression by a complex between the iron-responsive element of ferritin mRNA and its specific cytoplasmic binding protein is position-dependent in vivo.
    EMBO J. 1990 Dec;9(12):4127-33 PMID: 1701143
  23. Cooperative binding of R17 coat protein to RNA.
    Biochemistry. 1990 Dec 18;29(50):11051-7 PMID: 1703010
  24. Characteristics of the interaction of the ferritin repressor protein with the iron-responsive element.
    Biol Met. 1991;4(1):48-55 PMID: 1854587
  25. Ferritin mRNA probed, near the iron regulatory region, with protein and chemical (1,10-phenanthroline-Cu) nucleases. A possible role for base-paired flanking regions.
    Biol Met. 1991;4(1):56-61 PMID: 1854588
  26. Extension inhibition analysis of translation initiation complexes.
    Methods Enzymol. 1988;164:419-25 PMID: 2468068
  27. Unusual mRNA pseudoknot structure is recognized by a protein translational repressor.
    Cell. 1989 May 19;57(4):531-6 PMID: 2470510
  28. The iron-responsive element binding protein: a method for the affinity purification of a regulatory RNA-binding protein.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5768-72 PMID: 2474819
  29. A cytosolic protein binds to structural elements within the iron regulatory region of the transferrin receptor mRNA.
    Proc Natl Acad Sci U S A. 1989 May;86(10):3574-8 PMID: 2498873
  30. Purification of a specific repressor of ferritin mRNA translation from rabbit liver.
    J Biol Chem. 1989 Aug 15;264(23):13765-9 PMID: 2569464
  31. Iron regulation of transferrin receptor mRNA levels requires iron-responsive elements and a rapid turnover determinant in the 3' untranslated region of the mRNA.
    EMBO J. 1989 Dec 1;8(12):3693-9 PMID: 2583116
  32. Specific RNA binding by Q beta coat protein.
    Biochemistry. 1989 Jan 10;28(1):71-6 PMID: 2706270
  33. Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction.
    Science. 1989 Apr 21;244(4902):357-9 PMID: 2711187
  34. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency.
    Cell. 1985 Mar;40(3):515-26 PMID: 2982496
  35. Posttranscriptional regulatory mechanisms in Escherichia coli.
    Annu Rev Biochem. 1988;57:199-233 PMID: 3052271
  36. Messenger RNA structure and gene regulation at the translational level in Escherichia coli: the case of threonine:tRNAThr ligase.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7892-6 PMID: 3054873
  37. Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs.
    Proc Natl Acad Sci U S A. 1988 Apr;85(7):2171-5 PMID: 3127826
  38. The iron-responsive element is the single element responsible for iron-dependent translational regulation of ferritin biosynthesis. Evidence for function as the binding site for a translational repressor.
    J Biol Chem. 1988 Dec 15;263(35):19048-52 PMID: 3198610
  39. Translational repression in eukaryotes: partial purification and characterization of a repressor of ferritin mRNA translation.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9503-7 PMID: 3200835
  40. Autogenous regulatory site on the bacteriophage T4 gene 32 messenger RNA.
    J Mol Biol. 1988 Jun 5;201(3):517-35 PMID: 3262167
  41. RNA binding site of R17 coat protein.
    Biochemistry. 1987 Mar 24;26(6):1563-8 PMID: 3297131
  42. A stem-loop in the 3' untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm.
    Cell. 1988 Jun 3;53(5):815-25 PMID: 3370673
  43. Iron regulates ferritin mRNA translation through a segment of its 5' untranslated region.
    Proc Natl Acad Sci U S A. 1987 Dec;84(23):8478-82 PMID: 3479802
  44. Multiple red cell ferritin mRNAs, which code for an abundant protein in the embryonic cell type, analyzed by cDNA sequence and by primer extension of the 5'-untranslated regions.
    J Biol Chem. 1986 Jan 15;261(2):949-55 PMID: 3484480
  45. Defining the binding site of Xenopus transcription factor IIIA on 5S RNA using truncated and chimeric 5S RNA molecules.
    Nucleic Acids Res. 1987 Mar 25;15(6):2737-55 PMID: 3562234
  46. Noncoding 3' sequences of the transferrin receptor gene are required for mRNA regulation by iron.
    EMBO J. 1987 May;6(5):1287-93 PMID: 3608980
  47. Oligoribonucleotide synthesis using T7 RNA polymerase and synthetic DNA templates.
    Nucleic Acids Res. 1987 Nov 11;15(21):8783-98 PMID: 3684574
  48. Translational control of gene expression in a normal fibroblast. Characterization of a subclass of mRNAs with unusual kinetic properties.
    Biochemistry. 1986 Apr 22;25(8):2033-41 PMID: 3707930
  49. Influence of 5' proximal secondary structure on the translational efficiency of eukaryotic mRNAs and on their interaction with initiation factors.
    J Biol Chem. 1986 Oct 25;261(30):13979-89 PMID: 3771516
  50. Subunit dimers in sheep spleen apoferritin. The effect on iron storage.
    J Biol Chem. 1983 Oct 10;258(19):11719-26 PMID: 6619139
  51. Phytoferritin is synthesized in vitro as a high-molecular-weight precursor. Studies on the synthesis and the uptake in vitro of the precursors of ferritin and ferredoxin by intact chloroplasts.
    Biochem J. 1983 Sep 15;214(3):943-50 PMID: 6626165
  52. The effect of iron on the synthesis and amount of ferritin in red blood cells during ontogeny.
    J Biol Chem. 1981 Feb 25;256(4):1711-5 PMID: 6970197
  53. Iron(II)-ethylenediaminetetraacetic acid catalyzed cleavage of RNA and DNA oligonucleotides: similar reactivity toward single- and double-stranded forms.
    Biochemistry. 1990 Feb 13;29(6):1355-61 PMID: 2110477
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.10.4166
Published
1991-05-15
Pages
4166-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51619
Subset
IM
Grants
NIDDK NIH HHS · DK20251 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.10.4166 PMC Full Text View journal details
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