+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The beta-globin C-->G mutation at 6 bp 3' to the termination codon causes beta-thalassaemia by decreasing the mRNA level

The beta-globin C-->G mutation at 6 bp 3' to the termination codon causes beta-thalassaemia by decreasing the mRNA level

British Journal of Haematology 118(2): 671-676

We have studied the expression of the silent beta-thalassaemia term+6 (C-->G) mutation, at nucleotide 6 after the stop codon within the human beta-globin 3' untranslated regions (3'UTR), by stable transfection in murine erythroleukaemia (MEL) cells. Steady state mRNA levels from transfected MEL cells containing the term+6 mutant allele were reduced by 52-60%, compared with those obtained from the normal beta-globin gene, in both total and cytoplasmic RNA fractions, showing that the mutation itself is responsible for the similar data obtained from patients. Upon analysis of nuclear RNA, the term+6 mutation was found to also lower the ratio of cleaved/uncleaved transcripts by 22-30%, thus revealing that it interferes with correct 3'-end formation of beta-globin mRNA. The term+6 mutation lies within a polypyrimidine track, similar to that in the beta-intervening sequence II (beta-IVSII), which is known to be an important contributor to the promotion of premRNA 3'-end formation. We propose that the two polypyrimidine tracks flanking the translated region of exon III of the human beta-globin gene may co-operate during beta-globin mRNA biogenesis.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 047585436

Download citation: RISBibTeXText

PMID: 12139763

Related references

Development of K562 cell clones expressing beta-globin mRNA carrying the beta039 thalassaemia mutation for the screening of correctors of stop-codon mutations. Biotechnology and Applied Biochemistry 54(1): 41-52, 2009

HbF production in beta thalassaemia heterozygotes for the IVS-II-1 G-->A beta(0)-globin mutation. Implication of the haplotype and the (G)gamma-158 C-->T mutation on the HbF level. American Journal of Hematology 64(3): 151-155, 2000

Beta O-39 thalassemia gene: a premature termination codon causes beta-mRNA deficiency without affecting cytoplasmic beta-mRNA stability. Blood 64(1): 23-32, 1984

Intranuclear defect in beta-globin mRNA accumulation due to a premature translation termination codon. Blood 64(1): 13-22, 1984

Beta -Globin mRNA decay in erythroid cells: UG site-preferred endonucleolytic cleavage that is augmented by a premature termination codon. Proceedings of the National Academy of Sciences of the United States of America 99(20): 12741-6, 2002

A novel beta-globin mutation (HBB:c.107A>G; or codon 35 beta (A-->G)) at alpha-beta chain interfaces. Annals of Hematology 88(12): 1269-1271, 2009

Nonsense codon mutations in the terminal exon of the beta-globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant beta-thalassemia. Blood 83(8): 2031-2037, 1994

A novel frameshift mutation (+G) at codons 15/16 in a beta0 thalassaemia gene results in a significant reduction of beta globin mRNA values. Journal of Clinical Pathology 58(9): 923-926, 2005

A new beta zero-thalassaemia nonsense mutation (codon 112, T-->A) not associated with a dominant type of thalassaemia in the heterozygote. British Journal of Haematology 83(3): 523-524, 1993

A genetic combination of silent beta-thalassaemia, high Hb A2 beta-thalassaemia, and single alpha globin gene deletion causing mild thalassaemia intermedia. Journal of Medical Genetics 21(2): 153-156, 1984

Filipino beta zero thalassaemia: a high Hb A2 beta zero thalassaemia resulting from a large deletion of the 5' beta globin gene region. Journal of Medical Genetics 30(3): 240-244, 1993

A novel mutation in the beta-globin gene causing beta-thalassaemia in a Swedish family. European Journal of Haematology 57(2): 182-184, 1996

A novel beta-thalassaemia mutation in the 5' untranslated region of the beta-globin gene. British Journal of Haematology 88(2): 307-310, 1994

Decreased beta globin mRNA activity in bone marrow cells in homozygous and heterozygous beta thalassaemia. Nature: New Biology 244(139): 280-281, 1973

Australian beta zero-thalassaemia: a high haemoglobin A2 beta zero-thalassaemia due to a 12 kb deletion commencing 5' to the beta-globin gene. British Journal of Haematology 82(1): 107-113, 1992