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PMID: 7969150 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Erythroid cell-specific determinants of alpha-globin mRNA stability.

Molecular and cellular biology ·Vol. 14 ·No. 12 ·1994-12-00 ·Pages 8123-32

Weiss IM, Liebhaber SA

Abstract

Although globin mRNAs are considered prototypes of highly stable messages, the mechanisms responsible for their longevity remain largely undefined. As an initial step in identifying potential cis-acting elements or structures which contribute to their stability, we analyzed the defect in expression of a naturally occurring alpha 2-globin mutant, alpha Constant Spring (CS). The CS mutation is a single-base change in the translation termination codon (UAA-->CAA) that allows the ribosome to read through into the 3' nontranslated region (NTR). The presence of CS mRNA in transcriptionally active erythroid precursors and its absence (relative to normal alpha-globin mRNA) in the more differentiated transcriptionally silent erythrocytes suggest that this mutation disrupts some feature of the alpha-globin mRNA required for its stability. Using a transient transfection system, we demonstrate that in murine erythroleukemia cells the CS mRNA is unstable compared with the normal alpha 2-globin mRNA. The analyses of several other naturally occurring and site-directed mutant alpha-globin genes in murine erythroleukemia cells indicate that entry of a translating ribosome into the 3' NTR targets the message for accelerated degradation in erythroid cells. In contrast, both the CS and alpha 2-globin mRNAs are stable in several nonerythroid cell lines. These results suggest that translational readthrough disrupts a determinant associated with the alpha 2-globin 3' NTR which is required for mRNA stability in erythroid cells.

MeSH Terms
Animals Base Sequence DNA Primers/chemistry Erythroid Precursor Cells/metabolism Globins/genetics Hemoglobins, Abnormal/genetics In Vitro Techniques Mice Molecular Sequence Data Protein Biosynthesis RNA, Messenger/metabolism Ribosomes/metabolism Tumor Cells, Cultured
Chemicals
DNA Primers Hemoglobins, Abnormal RNA, Messenger Globins Hemoglobin Constant Spring
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Weiss I M
Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia 19104.
Liebhaber S A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.12.8123-8132.1994
Published
1994-12-00
Pages
8123-32
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359351
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.12.8123-8132.1994 PMC Full Text View journal details
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