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PMID: 4018033 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The EMBO journal ·Vol. 4 ·No. 2 ·1985-02-00 ·Pages 453-6

Orkin SH, Cheng TC, Antonarakis SE, Kazazian HH

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.

MeSH Terms
Base Sequence Genes Globins/genetics Humans Mutation Poly A/genetics RNA Processing, Post-Transcriptional RNA, Messenger/genetics Thalassemia/genetics Transcription, Genetic
Chemicals
RNA, Messenger Poly A Globins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Orkin S H
Cheng T C
Antonarakis S E
Kazazian H H
References (24)
24 references, click to expand
  1. Steps in the processing of Ad2 mRNA: poly(A)+ nuclear sequences are conserved and poly(A) addition precedes splicing.
    Cell. 1978 Dec;15(4):1477-93 PMID: 729004
  2. Sequencing end-labeled DNA with base-specific chemical cleavages.
    Methods Enzymol. 1980;65(1):499-560 PMID: 6246368
  3. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping.
    Methods Enzymol. 1980;65(1):718-49 PMID: 6154876
  4. The primary transcription unit of the mouse beta-major globin gene.
    Cell. 1981 Feb;23(2):585-93 PMID: 6937266
  5. The sequence 5'-AAUAAA-3'forms parts of the recognition site for polyadenylation of late SV40 mRNAs.
    Cell. 1981 Apr;24(1):251-60 PMID: 6113054
  6. Transcription units of adenovirus type 2. Termination of transcription beyond the poly(A) addition site in early regions 2 and 4.
    J Mol Biol. 1980 Dec 15;144(3):377-86 PMID: 7253021
  7. Linkage of beta-thalassaemia mutations and beta-globin gene polymorphisms with DNA polymorphisms in human beta-globin gene cluster.
    Nature. 1982 Apr 15;296(5858):627-31 PMID: 6280057
  8. The end of the message.
    Nature. 1982 Aug 5;298(5874):516-7 PMID: 7099250
  9. Globin RNA transcription: a possible termination site and demonstration of transcriptional control correlated with altered chromatin structure.
    Cell. 1982 Jul;29(3):887-93 PMID: 7151174
  10. A single-base change at a splice site in a beta 0-thalassemic gene causes abnormal RNA splicing.
    Cell. 1982 Jul;29(3):903-11 PMID: 7151176
  11. Specific transcription and RNA splicing defects in five cloned beta-thalassaemia genes.
    Nature. 1983 Apr 14;302(5909):591-6 PMID: 6188062
  12. A precise termination site in the mouse beta major-globin transcription unit.
    Proc Natl Acad Sci U S A. 1983 Aug;80(15):4694-8 PMID: 6192441
  13. Nucleotide sequence analysis of the delta beta-globin gene region in humans.
    J Biol Chem. 1983 Oct 10;258(19):11599-609 PMID: 6311816
  14. Inhibition of RNA cleavage but not polyadenylation by a point mutation in mRNA 3' consensus sequence AAUAAA.
    Nature. 1983 Oct 13-19;305(5935):600-5 PMID: 6194440
  15. Alpha-thalassaemia caused by a polyadenylation signal mutation.
    Nature. 1983 Nov 24-30;306(5941):398-400 PMID: 6646217
  16. Analysis of processing and polyadenylation signals of the hepatitis B virus surface antigen gene by using simian virus 40-hepatitis B virus chimeric plasmids.
    Mol Cell Biol. 1983 Dec;3(12):2250-8 PMID: 6318092
  17. The end of the message and beyond.
    Nature. 1984 Feb 2-8;307(5950):412-3 PMID: 6694735
  18. Site-specific polyadenylation in a cell-free reaction.
    Cell. 1984 Mar;36(3):581-91 PMID: 6230155
  19. beta-Thalassemia in American Blacks: novel mutations in the "TATA" box and an acceptor splice site.
    Proc Natl Acad Sci U S A. 1984 Feb;81(4):1154-8 PMID: 6583702
  20. Are U4 small nuclear ribonucleoproteins involved in polyadenylation?
    Nature. 1984 May 10-16;309(5964):179-82 PMID: 6325940
  21. A precise termination site in the mouse beta-major globin transcription unit.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):2274 PMID: 6371812
  22. Requirement for the 3' flanking region of the bovine growth hormone gene for accurate polyadenylylation.
    Proc Natl Acad Sci U S A. 1984 Jul;81(13):3944-8 PMID: 6146135
  23. Requirement of a downstream sequence for generation of a poly(A) addition site.
    Cell. 1984 Jul;37(3):993-9 PMID: 6744418
  24. The mutation and polymorphism of the human beta-globin gene and its surrounding DNA.
    Annu Rev Genet. 1984;18:131-71 PMID: 6084979
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1985-02-00
Pages
453-6
Language
English
Region
England
NLM ID
8208664
PMCID
PMC554207
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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