Nonsense mutations in the human beta-globin gene affect mRNA metabolism.
AUTOR(ES)
Baserga, S J
RESUMO
A number of premature translation termination mutations (nonsense mutations) have been described in the human alpha- and beta-globin genes. Studies on mRNA isolated from patients with beta zero-thalassemia have shown that for both the beta-17 and the beta-39 mutations less than normal levels of beta-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human beta-globin mRNA.) In vitro studies using the cloned beta-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. We have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, we have studied the effect of five nonsense mutations and two missense mutations on the expression of human beta-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=279927Documentos Relacionados
- Nonsense codons in human beta-globin mRNA result in the production of mRNA degradation products.
- The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor.
- Beta-globin nonsense mutation: deficient accumulation of mRNA occurs despite normal cytoplasmic stability.
- Sequence organization of the beta-globin mRNA precursor.
- Sequence of the rat beta-globin mRNA.