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

TitleThe beta-globin C-->G mutation at 6 bp 3' to the termination codon causes beta-thalassaemia by decreasing the mRNA level.
Publication TypeJournal Article
Year of Publication2002
AuthorsSgourou, A, Papachatzopoulou, A, Psiouri, L, Antoniou, M, Zoumbos, N, Gibbs, RA, Athanassiadou, A
JournalBr J Haematol
Volume118
Issue2
Pagination671-6
Date Published2002 Aug
ISSN0007-1048
Keywordsbeta-Thalassemia, Child, Codon, Terminator, Globins, Humans, Male, Mutation, RNA, Messenger, Transfection
Abstract

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.

Alternate JournalBr. J. Haematol.
PubMed ID12139763