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Title: Premature translation termination mediates triosephosphate isomerase mRNA degradation

Abstract

The authors 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 condon and generated a protein of 188 amino acids, instead of the usual 248 amino acids. To determine how mRNA primary structure and translation and 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.

Authors:
;
Publication Date:
Research Org.:
Dept. of Human Genetics, Roswell Park Memorial Institute, Buffalo, NY 14263 (US)
OSTI Identifier:
5142689
Resource Type:
Journal Article
Journal Name:
Mol. Cell. Biol.; (United States)
Additional Journal Information:
Journal Volume: 8:2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ISOMERASES; GENES; MESSENGER-RNA; MUTATIONS; STRUCTURE-ACTIVITY RELATIONSHIPS; RNA PROCESSING; ANEMIAS; MODIFICATIONS; PROTEINS; DISEASES; ENZYMES; HEMIC DISEASES; NUCLEIC ACIDS; ORGANIC COMPOUNDS; RNA; SYMPTOMS; 550200* - Biochemistry; 550400 - Genetics

Citation Formats

Daar, I O, and Maquat, L E. Premature translation termination mediates triosephosphate isomerase mRNA degradation. United States: N. p., 1988. Web. doi:10.1128/MCB.8.2.802.
Daar, I O, & Maquat, L E. Premature translation termination mediates triosephosphate isomerase mRNA degradation. United States. doi:10.1128/MCB.8.2.802.
Daar, I O, and Maquat, L E. Mon . "Premature translation termination mediates triosephosphate isomerase mRNA degradation". United States. doi:10.1128/MCB.8.2.802.
@article{osti_5142689,
title = {Premature translation termination mediates triosephosphate isomerase mRNA degradation},
author = {Daar, I O and Maquat, L E},
abstractNote = {The authors 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 condon and generated a protein of 188 amino acids, instead of the usual 248 amino acids. To determine how mRNA primary structure and translation and 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.},
doi = {10.1128/MCB.8.2.802},
journal = {Mol. Cell. Biol.; (United States)},
number = ,
volume = 8:2,
place = {United States},
year = {1988},
month = {2}
}