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PMID: 2573525 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Novel metabolism of several beta zero-thalassemic beta-globin mRNAs in the erythroid tissues of transgenic mice.

The EMBO journal ·Vol. 8 ·No. 9 ·1989-09-00 ·Pages 2613-9

Lim S, Mullins JJ, Chen CM, Gross KW, Maquat LE

Abstract

Mice that are transgenic for human beta zero-thalassemic beta-globin alleles were generated in order to study how beta zero-thalassemic mutations affect beta-globin RNA metabolism in erythroid tissues. Three thalassemic alleles were studied, each of which harbors either a frameshift or a nonsense mutation. These mutations result in the premature termination of beta-globin mRNA translation and an abnormally low level of beta-globin mRNA in the peripheral blood of thalassemic patients. Comparative studies of mice that express any of the beta zero-thalassemic transgenes with mice that express a normal human beta-globin transgene demonstrated that all three thalassemic mRNAs are metabolized in erythroid tissues abnormally. RNA blotting and S1 nuclease transcript mapping revealed for each thalassemic transgene that (i) the full-length mRNA is abnormally short-lived and (ii) in addition to full-length mRNA, three more stable yet smaller RNAs are present. These smaller RNAs are polyadenylated and lack the mRNA 5' end.

MeSH Terms
Animals Cell Nucleus/metabolism Cytoplasm/metabolism Erythrocytes/metabolism Exons Globins/genetics Humans Italy Jews/genetics Mice Mice, Transgenic Plasmids Poly A/metabolism RNA, Messenger/metabolism Spleen/metabolism Terminator Regions, Genetic Thalassemia/genetics Transfection Turkey
Chemicals
RNA, Messenger Poly A Globins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lim S
Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, NY 14263.
Mullins J J
Chen C M
Gross K W
Maquat L E
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1989-09-00
Pages
2613-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC401267
Subset
IM
Grants
NHLBI NIH HHS · HL35792 · United States
NIGMS NIH HHS · R01 GM30248 · United States
External Links
PubMed source PMC Full Text View journal details
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