Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene.

S. H. Orkin, T. C. Cheng, S. E. Antonarakis, Haig Kazazian

Research output: Contribution to journalArticle

Abstract

A beta-globin gene cloned from a person with beta-thalassemia contained a T----C substitution within the conserved sequence AATAAA that forms a portion of the recognition signal for endonucleolytic cleavage and polyadenylation of primary mRNA transcripts. By Northern blot analysis a novel beta-globin RNA species, 1500 nucleotides in length, was detected in erythroid RNA. Nuclease protection studies of erythroid RNA, as well as RNA generated upon transient expression of the cloned mutant gene in HeLa cells, located the 3' terminus of this novel, polyadenylated RNA 900 nucleotides downstream of the normal poly(A) addition site, within 15 nucleotides of the first AATAAA in the 3'-flanking region of the beta-globin gene. These findings define the in vivo terminus of an elongated RNA and establish that human beta-globin transcription may extend at least 900 nucleotides 3' of the normal polyadenylation site.

Original languageEnglish (US)
Pages (from-to)453-456
Number of pages4
JournalEMBO Journal
Volume4
Issue number2
StatePublished - Feb 1985
Externally publishedYes

Fingerprint

Polyadenylation
beta-Globins
Thalassemia
Genes
RNA
Nucleotides
Mutation
3' Flanking Region
Messenger RNA
Poly A
Conserved Sequence
beta-Thalassemia
Transcription
HeLa Cells
Northern Blotting
Substitution reactions

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. / Orkin, S. H.; Cheng, T. C.; Antonarakis, S. E.; Kazazian, Haig.

In: EMBO Journal, Vol. 4, No. 2, 02.1985, p. 453-456.

Research output: Contribution to journalArticle

Orkin, S. H. ; Cheng, T. C. ; Antonarakis, S. E. ; Kazazian, Haig. / Thalassemia due to a mutation in the cleavage-polyadenylation signal of the human beta-globin gene. In: EMBO Journal. 1985 ; Vol. 4, No. 2. pp. 453-456.
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