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PMID: 2832737 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Premature translation termination mediates triosephosphate isomerase mRNA degradation.

Molecular and cellular biology ·Vol. 8 ·No. 2 ·1988-02-00 ·Pages 802-13

Daar IO, Maquat LE

Abstract

We characterized an anemia-inducing mutation in the human gene for triosephosphate isomerase (TPI) that resulted in the production of prematurely terminated protein and mRNA with a reduced cytoplasmic half-life. The mutation converted a CGA arginine codon to a TGA nonsense codon and generated a protein of 188 amino acids, instead of the usual 248 amino acids. To determine how mRNA primary structure and translation influence mRNA stability, in vitro-mutagenized TPI alleles were introduced into cultured L cells and analyzed for their effect on TPI RNA metabolism. Results indicated that mRNA stability is decreased by all nonsense and frameshift mutations. To determine the relative contribution of the changes in mRNA structure and translation to the altered half-life, the effects of individual mutations were compared with the effects of second-site reversions that restored translation termination to normal. All mutations that resulted in premature translation termination reduced the mRNA half-life solely or mainly by altering the length of the mRNA that was translated. The only mutation that altered translation termination and that reduced the mRNA half-life mainly by affecting the mRNA structure was an insertion that shifted termination to a position downstream of the normal stop codon.

MeSH Terms
Alleles Amino Acid Sequence Animals Base Sequence Carbohydrate Epimerases/genetics Cell Line DNA Restriction Enzymes Genes Humans Molecular Sequence Data Mutation Peptide Chain Termination, Translational Plasmids RNA, Messenger/genetics,metabolism Triose-Phosphate Isomerase/genetics
Chemicals
RNA, Messenger DNA Restriction Enzymes Carbohydrate Epimerases Triose-Phosphate Isomerase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Daar I O
Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, New York 14263.
Maquat L E
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.8.2.802-813.1988
Published
1988-02-00
Pages
802-13
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC363207
Subset
IM
Grants
NIADDK NIH HHS · AM/GM 33938 · United States
NIDDK NIH HHS · DK 33938 · United States
NIADDK NIH HHS · R01 AM31747 · United States
External Links
PubMed source DOI: 10.1128/mcb.8.2.802-813.1988 PMC Full Text View journal details
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