Functional messenger RNA for human hemoglobin synthesis was prepared from reticulocyte lysates of patients with homozygous beta thalassemia and sickle cell anemia. The messenger RNA stimulated the synthesis of human globin chains by a cell-free system derived from Krebs mouse ascites cells. In the presence of beta thalassemia messenger RNA, the system synthesized much less beta chain than alpha chain whereas in the presence of sickle cell anemia messenger RNA, nearly equal amounts of alpha and beta chains were synthesized. The beta/alpha synthetic ratios obtained in the cell-free system were similar to those obtained by incubating intact beta thalassemia and sickle cell anemia reticulocytes in the presence of radioactive leucine. The experiments provide direct evidence of a defect in messenger RNA for beta chains as a cause for the decreased synthesis of beta chains observed in beta thalassemia.
Edward J. Benz Jr., Bernard G. Forget
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JD Stone, AS Chervin, DH Aggen, DM Kranz |
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Annual Review of Genomics and Human Genetics | 2012 |
Milestones in the History of Hemoglobin Research (In Memory of Professor Titus H.J. Huisman)
SL Thein |
Hemoglobin | 2011 |
Thalassemia: An Overview of 50 Years of Clinical Research
VG Sankaran, DG Nathan |
Hematology/Oncology Clinics of North America | 2010 |
Ninth Cooley's Anemia Symposium: summary and perspective
AW Nienhuis |
Annals of the New York Academy of Sciences | 2010 |
History of genetic disease: Thalassaemia: the long road from bedside to genome
DJ Weatherall |
Nature Reviews Genetics | 2004 |
2003 William Allan Award address. The Thalassemias: the role of molecular genetics in an evolving global health problem
D Weatherall |
The American Journal of Human Genetics | 2004 |
The Thalassemias: The Role of Molecular Genetics in an Evolving Global Health Problem* *Previously presented at the annual meeting of The American Society of Human Genetics, in Los Angeles, on November 7, 2003
D Weatherall |
The American Journal of Human Genetics | 2004 |
The thalassemia syndromes: lessons from molecular medicines index case
EJ Benz |
Transactions of the American Clinical and Climatological Association | 1996 |
Advances in Human Genetics
H Harris, K Hirschhorn |
1990 | |
Selective expression of an erythroid-specific isoform of protein 4.1
TK Tang, TL Leto, I Correas, MA Alonso, VT Marchesi, EJ Benz |
Proceedings of the National Academy of Sciences | 1988 |
Molecular Biology of Hemopoiesis
M Tavassoli, ED Zanjani, JL Ascensao, NG Abraham, AS Levine |
1988 | |
Beta zero thalassemia caused by a base substitution that creates an alternative splice acceptor site in an intron
JE Metherall, FS Collins, J Pan, SM Weissman, BG Forget |
The EMBO Journal | 1986 |
β Globin messenger RNA content of bone marrow erythroblasts in heterozygous β-thalassemia
EJ Benz, J Pritchard, D Hillman, J Glass, BG Forget |
American Journal of Hematology | 1984 |
The aminoacyl-tRNA population of human reticulocytes
D Hatfield, F Varricchio, M Rice, BG Forget |
The Journal of biological chemistry | 1982 |
Molecular analysis of the beta-thalassemia phenotype associated with inheritance of hemoglobin E (alpha 2 beta2(26)Glu leads to Lys)
EJ Benz, BW Berman, BL Tonkonow, E Coupal, T Coates, LA Boxer, A Altman, JG 3rd |
Journal of Clinical Investigation | 1981 |
Posttranscriptional defects in beta-globin messenger RNA metabolism in beta-thalassemia: abnormal accumulation of beta-messenger RNA precursor sequences
EJ Benz, AL Scarpa, BL Tonkonow, HA Pearson, AK Ritchey |
Journal of Clinical Investigation | 1981 |
REGULATION OF GLOBIN GENE EXPRESSION AT THE MOLECULAR LEVEL
WF Anderson |
Annals of the New York Academy of Sciences | 1980 |
Processing of human beta-globin mRNA precursor to mRNA is defective in three patients with beta+-thalassemia
LE Maquat, AJ Kinniburgh, LR Beach, GR Honig, J Lazerson, WB Ershler, J Ross |
Proceedings of the National Academy of Sciences | 1980 |
Disorders of Human Hemoglobin
A Bank, JG Mears, F Ramirez |
Science | 1980 |
The molecular basis of disorders of human hemoglobin synthesis
F Ramirez, JG Mears, A Bank |
Molecular and Cellular Biochemistry | 1980 |
Recent developments in the molecular genetics of human hemoglobin
DJ Weatherall, JB Clegg |
Cell | 1979 |
The Molecular Biology of the Thalassemia Syndromes
A Bank, F Ramirez, WF Anderson |
Critical Reviews in Biochemistry and Molecular Biology | 1978 |
Variability in the amount of β-globin mRNA in β0 thalassemia
EJ Benz, BG Forget, DG Hillman, M Cohen-Solal, J Pritchard, C Cavallesco, W Prensky, D Housman |
Cell | 1978 |
Comparison of Haematological Features of the β0and β+Thalassaemia Traits in Jamaican Negroes
DP Millard, K Mason, BE Serjeant, GR Serjeant |
British Journal of Haematology | 1977 |
Relative stability of alpha- and beta-globin messenger RNAs in homozygous beta+ thalassemia
AW Nienhuis, P Turner, EJ Benz |
Proceedings of the National Academy of Sciences | 1977 |
Authentic beta-globin mRNA sequences in homozygous betaO-thalassemia
GF Temple, JC Chang, YW Kan |
Proceedings of the National Academy of Sciences | 1977 |
Molecular Mechanisms of Protein Biosynthesis
DA Shafritz |
Molecular Mechanisms of Protein Biosynthesis | 1977 |
Human beta-globin messenger RNA. II. nucleotide sequences derived from 125I-labeled globin messenger RNA
M Cohen-Solal, BG Forget, W Prensky, CA Marotta, SM Weissman |
The Journal of biological chemistry | 1977 |
Human beta-globin messenger RNA. III. Nucleotide sequences derived from complementary DNA
CA Marotta, JT Wilson, BG Forget, SM Weissman |
The Journal of biological chemistry | 1977 |
Human beta-globin messenger RNA. I. Nucleotide sequences derived from complementary RNA
CA Marotta, BG Forget, M Cohne-Solal, JT Wilson, SM Weissman |
The Journal of biological chemistry | 1977 |
Assay of Thalassaemic Messenger RNA in the Wheat Germ System
J Pritchard, J Longley, JB Clegg, DJ Weatherall |
British Journal of Haematology | 1976 |
Abnormal or absent β mRNA in β0 Ferrara and gene deletion in δβ thalassaemia
F Ramirez, JV O'Donnell, PA Marks, A Bank, S Musumeci, G Schilirò, G Pizzarelli, G Russo, B Luppis, R Gambino |
Nature | 1976 |
Absence of messenger RNA and gene DNA for β-globin chains in hereditary persistence of fetal hemoglobin
BG Forget, DG Hillman, H Lazarus, EF Barell, EJ Benz, CT Caskey, TH Hulsman, WA Schroeder, D Housman |
Cell | 1976 |
Globin synthesis in fractionated Normoblasts of beta-thalassemia heterozygotes
WG Wood, G Stamatoyannopoulos |
Journal of Clinical Investigation | 1975 |
Molecular Basis of Thalassaemia
DJ Weatherall, JB Clegg |
British Journal of Haematology | 1975 |
Relative numbers of human globin genes assayed with purified alpha and beta complementary human DNA
F Ramirez, C Natta, JV O'Donnell, V Canale, G Bailey, T Sanguensermsri, GM Maniatis, PA Marks, A Bank |
Proceedings of the National Academy of Sciences | 1975 |
Further evidence of a quantitative deficiency of chain-specific globin mRNA in the thalassemia syndromes
HH Kazazian, GD Ginder, PG Snyder, RJ van Beneden, AP Woodhead |
Proceedings of the National Academy of Sciences | 1975 |
Human globin gene analysis for a patient with beta-o/delta beta-thalassemia
S Ottolenghi, WG Lanyon, R Williamson, DJ Weatherall, JB Clegg, CS Pitcher |
Proceedings of the National Academy of Sciences | 1975 |
Synthesis of DNA complementary to separated human alpha and beta globin messenger RNAs
BG Forget, D Housman, EJ Benz, RP McCaffrey |
Proceedings of the National Academy of Sciences | 1975 |
Separation of low molecular weight RNA by polyacrylamide gel electrophoresis
F Varricchio, HJ Ernst |
Analytical Biochemistry | 1975 |
Translational Control of Hemoglobin Synthesis in Thalassemic Bone Marrow
G Cividalli, DG Natham, HF Lodish |
Journal of Clinical Investigation | 1974 |
Imbalance in α and β Globin Synthesis Associated with a Hemoglobinopathy
RF Rieder, GW 3rd |
Journal of Clinical Investigation | 1974 |
THE CLINICAL AND CHEMICAL HETEROGENEITY OF THE ?-THALASSEMIAS
DJ Weatherall, JB Clegg, AV Roberts, HH Knox |
Annals of the New York Academy of Sciences | 1974 |
DECREASED GLOBIN MESSENGER RNA IN THALASSEMIA BY HYBRIDIZATION AND BIOLOGIC ACTIVITY ASSAYS
R Gambino, DL Kacian, F Ramirez, LW Dow, E Grossbard, C Natta, S Spiegelman, PA Marks, A Bank |
Annals of the New York Academy of Sciences | 1974 |
The Molecular Basis of Thalassemi
BG Forget, WF Anderson |
Critical Reviews in Biochemistry and Molecular Biology | 1974 |
VARIATION IN ?/? SYNTHESIS RATIOS IN THALASSEMIA AND HEMOGLOBINOPATHIES
RF Rieder |
Annals of the New York Academy of Sciences | 1974 |
GLOBIN TRANSLATION IN THALASSEMIC BONE MARROW
DG Nathan, G Cividalli, HF Lodish |
Annals of the New York Academy of Sciences | 1974 |
GLOBIN MESSENGER RNA IN THE THALASSEMIA SYNDROMES
BG Forget, D Baltimore, EJ Benz, D Housman, P Lebowitz, CA Marotta, RP McCaffrey, A Skoultchi, PS Swerdlow, IM Verma, SM Weissman |
Annals of the New York Academy of Sciences | 1974 |
Gene deletion as the cause of α thalassaemia: The severe form of α thalassaemia is caused by a haemoglobin gene deletion
S Ottolenghi, WG Lanyon, J Paul, R Williamson, DJ Weatherall, JB Clegg, J Pritchard, S Pootrakul, WH Boon |
Nature | 1974 |
Absence of Messenger RNA for Beta Globin Chain in β°-Thalassaemia
BG Forget, EJ Benz, A Skoultchi, C Baglioni, D Housman |
Nature | 1974 |
REGULATION OF GLOBIN SYNTHESIS IN THE THALASSEMIAS
A Bank, R Gambino, F Ramirez, G Maniatis, C Natta, D Kacian, S Spiegelman, PA Marks |
Annals of the New York Academy of Sciences | 1974 |
The genetic control of protein synthesis: The haemoglobin model
DJ Weatherall |
Journal of clinical pathology. Supplement (Royal College of Pathologists) | 1974 |
A limited number of globin genes in human DNA
R Gambino, D Kacian, J O'Donnell, F Ramirez, PA Marks, A Bank |
Proceedings of the National Academy of Sciences | 1974 |
Molecular basis for some disorders of haemoglobin synthesis. II
DJ Weatherall |
British medical journal | 1974 |
Cell-free transcription of mammalian chromatin: transcription of globin messenger RNA sequences from bone-marrow chromatin with mammalian RNA polymerase
AW Steggles, GN Wilson, JA Kantor, DJ Picciano, AK Falvey, WF Anderson |
Proceedings of the National Academy of Sciences | 1974 |
Nucleotide sequences of human globin messenger RNA
CA Marotta, BG Forget, SM Weissman, IM Verma, RP McCaffrey, D Baltimore |
Proceedings of the National Academy of Sciences | 1974 |
USE OF GLOBIN cDNA AS A HYBRIDIZATION PROBE FOR GLOBIN mRNA
D Housman, A Skoultchi, BG Forget, EJ Benz |
Annals of the New York Academy of Sciences | 1974 |
NUCLEOTIDE SEQUENCES OF HUMAN GLOBIN MESSENGER RNA
BG Forget, CA Marotta, SM Weissman, IM Verma, RP McCaffrey, D Baltimore |
Annals of the New York Academy of Sciences | 1974 |
Regulation of specific gene expression during embryonic development: Synthesis of globin messenger RNA during red cell formation in chick embryos
LN Chan, M Wiedmann, VM Ingram |
Developmental Biology | 1974 |
The Red Blood Cell
GJ Brewer |
The Red Blood Cell | 1974 |
On the structure of the hemoglobins A, A2, and F in a Negro with homozygous β-thalassemia
WA Schroeder, TH Huisman, JR Shelton, G Apell, JB Shelton, AR Brodie, CL Luicher, MH Blunt, A Miller |
Biochemical Medicine | 1974 |
Evidence for Nontranslated Messenger Ribonucleic Acid in Membrane-bound and Free Polysomes of Rabbit Liver
DA Shafritz |
The Journal of biological chemistry | 1974 |
Polyadenylate Sequences and Biologic Activity of Human Globin Messenger Ribonucleic Acid
A Cann, R Gambino, J Banks, A Bank |
The Journal of biological chemistry | 1974 |
The Separation and Identification of α- and β-Globin Messenger Ribonucleic Acids
MR Morrison, SA Brinkley, J Gorski, JB Lingrel |
The Journal of biological chemistry | 1974 |
Hemoglobin Messenger RNA from Human Bone Marrow ISOLATION AND TRANSLATION IN HOMOZYGOUS AND HETEROZYGOUS β-THALASSEMIA
AW Nienhuis, PH Canfield, WF Anderson |
Journal of Clinical Investigation | 1973 |
Decreased globin messenger RNA in thalassemia detected by molecular hybridization
DL Kacian, R Gambino, LW Dow, E Grossbard, C Natta, F Ramirez, S Spiegelman, PA Marks, A Bank |
Proceedings of the National Academy of Sciences | 1973 |
Quantitative deficiency of chain-specific globin messenger ribonucleic acids in the thalassemia syndromes
D Housman, BG Forget, A Skoultchi, EJ Benz |
Proceedings of the National Academy of Sciences | 1973 |
Effects of 5-bromo-2' -deoxyuridine on production of globin messenger RNA in dimethyl sulfoxide-stimulated Friend leukemia cells
HS Preisler, D Housman, W Scher, C Friend |
Proceedings of the National Academy of Sciences | 1973 |
Thalassemia: A Progress Report on Applied Molecular Biology
DG Nathan |
New England Journal of Medicine | 1973 |
Initiation of Globin Synthesis in β-Thalassemia
RG Crystal, NA Elson, A Nienhuis, AC Thornton, WF Anderson |
New England Journal of Medicine | 1973 |
The Differential Diagnosis of Hemolytic Anemias
N Costea |
Medical Clinics of North America | 1973 |
The Thalassemia Syndromes and the Intracellular Regulation of Globin Synthesis
A Bank, PA Marks |
Medical Clinics of North America | 1973 |
Decreased α Globin Messenger RNA Activity associated with Polyribosomes in α Thalassaemia
E Grossbard, M Terada, LW Dow, A Bank |
Nature: New biology | 1973 |
Translation of Liver Messenger Ribonucleic Acid in a Messenger-dependent Reticulocyte Cell-free System
DA Shafritz, JW Drysdale, KJ Isselbacher |
The Journal of biological chemistry | 1973 |
Thalassemia
D Deykin, C Balko, DG Nathan |
New England Journal of Medicine | 1972 |
Messenger RNA in animal cells
R Williamson |
Journal of medical genetics | 1972 |
Distinction between Two Types of Beta-Thalassaemia by Inducibility of the Cell-free Synthesis of Beta-Chains by Nonthalassaemic Soluble Fraction
PT Rowley, B Kosciolek |
Nature: New biology | 1972 |
Separation of α- and β-Globin Messenger RNAs
HH Kazazian |
Nature: New biology | 1972 |
Peptide Analysis of the Mouse Hemoglobin Messenger Ribonucleic Acid-directed Products Synthesized in Mammalian and Avian Cell-free Systems
RF Jones, JB Lingrel |
The Journal of biological chemistry | 1972 |