Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes.

Shakin, S H; Liebhaber, Stephen A.

doi:10.1172/jci112670

Cited by 31 publications

(15 citation statements)

References 29 publications

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“…It has been demonstrated that the ca2 gene encodes a 2to 3-fold higher steady state level of mRNA than the downstream al gene (Orkin and Goff, 1981;Liebhaber and Kan, 1983;Liebhaber et al, 1985). These levels are also reflected in the protein products of the two genes Shakin and Liebhaber, 1986). The promoters of both a globin genes are identical and their polyadenylation sites are not significantly dissimilar.…”

Section: Discussionmentioning

confidence: 99%

A pause site for RNA polymerase II is associated with termination of transcription.

et al. 1991

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Termination of transcription by RNA polymerase II has been postulated to involve a pausing process. We have identified such a pause signal, 350 bp into the 3′ flanking region of the human alpha 2 globin gene at a position where termination is thought to occur. We show that this pause signal enhances the utilization of an upstream poly(A) site which is otherwise out‐competed by a stronger downstream poly(A) site. We also demonstrate that the pause site rescues a poly(A) site that is inactive due to its location within an intron. Using nuclear run‐on analysis we show that elongating RNA polymerase II molecules accumulate over this pause signal. Furthermore we show that when the pause site is positioned immediately downstream of a strong poly(A) signal, significant levels of transcription termination take place.

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Section: Discussionmentioning

confidence: 99%

A pause site for RNA polymerase II is associated with termination of transcription.

et al. 1991

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“…Two studies, conducted in the early 1980s, have suggested that in normal persons the amount of a2-mRNA exceeds that of al-mRNA by a factor of 1.5 to 3. perhaps because of a decreased transcription of the alglobin gene (Liebhaber & Kan, 1981: Orkin & Goff, 1981. In a later study, Shakin & Liebhaber (1986) obtained some evidence for an equal translation of the two mRNAs and, based on the higher mRNA levels in reticulocytes, assumed a dominant role for the a2-gIobin gene. suggested that this might be the result of an N 3-fold excess of a2globin mFWA and an N 3-fold higher translational efficiency of the al-globin mRNA, perhaps based on the different structures of the 3' non-coding regions of the two genes.…”

Section: Mutationmentioning

confidence: 93%

The differences in quantities of α2‐and α1‐globin gene variants in heterozygotes

1994

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We have identified through sequencing of amplified DNA the mutations in the alpha 2- and alpha 1-globin genes in 63 individuals with a heterozygosity for an alpha chain abnormal haemoglobin (Hb). Moreover, we developed a reverse transcription/polymerase chain reaction (RT/PCR) based procedure for the determination of the alpha 2- and alpha 1-mRNA ratio in normal individuals. The numbers of alpha 2 and alpha 1 variants were nearly the same. The average percentage of the abnormal Hb in heterozygotes with alpha 2 mutations (23.5%) was slightly higher than that in heterozygotes with alpha 1 mutations (19.7%) (stable Hbs only). These percentages correspond to a ratio of alpha 2 to alpha 1 of 1.19 to 1 at the protein level. Variations in the number of active alpha-globin genes and in the stability of the variants (greatly) affected the percentages of the abnormal protein. The average ratio between the alpha 2- and alpha 1-mRNAs in 12 normal individuals was 2.6-2.75 to 1, about as expected from published data, and 2.0 to 1 for two persons with an alpha-thalassaemia-2 (alpha-thal-2) (-3.7 kb) heterozygosity. The high relative mRNA (alpha 2) level which is about twice the relative level of the alpha 2 protein suggests a less efficient translation of the alpha 2-mRNA.

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“…The α 2 -globin gene seems to have a dominant expression role over α 1 as it encodes approximately 2.6-fold more protein than α 1 [3]. However, recent studies on the expression of the α 1 - and α 2 -globin genes by Molchanova et al [4] have demonstrated that the output of the α 2 -variants is only 1.19 times higher than that of α 1 -variants in heterozygotes with four α-globin genes.…”

Section: Introductionmentioning

confidence: 99%

α-Thalassemia in the United Arab Emirates

El-Kalla

Baysal²

1998

Acta Haematol

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A neonatal screening survey of α-thalassemia (α-thal) among the United Arab Emirates (UAE) nationals was conducted on 418 consecutive cord blood samples. Our findings demonstrate that 49% of the cases studied were found with an α-globin gene defect. The gene frequency of the –α^3.7 was 0.2847 and that of the –α^4.2 was 0.0072. Four nondeletional α-thal mutations were found; α^PA-1, α^PA-2, Hb CS and α^-5nt del with gene frequencies of 0.0036, 0.0012, 0.0024, and 0.0072, respectively. We also report here the genotype-phenotype correlation in 22 patients with Hb H disease or Hb H-like syndrome. Of these, 6 were homozygous for the α^PA-1 mutation, 2 were homozygous for Hb CS, and 14 were compound heterozygous for either α^PA-1, Hb CS, α^-5nt del or ––MED-I, with the –α^3.7. The data reported here demonstrate that a considerable heterogeneity of α-thal mutations occurs in the UAE and that the incidence of α-thal in the indigenous population is one of the highest in the world. Our clinical data suggest that Hb H disease in the UAE has, in general, a mild to moderate phenotypic presentation.

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Translational profiles of alpha 1-, alpha 2-, and beta-globin messenger ribonucleic acids in human reticulocytes.

Cited by 31 publications

References 29 publications

A pause site for RNA polymerase II is associated with termination of transcription.

A pause site for RNA polymerase II is associated with termination of transcription.

The differences in quantities of α2‐and α1‐globin gene variants in heterozygotes

α-Thalassemia in the United Arab Emirates

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