Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase

Edward Chu, David Koeller, John L. Casey, James C. Drake, Bruce A. Chabner, Patrick C. Elwood, Sydelle Zinn, Carmen J. Allegra

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

Thymidylate synthase (TS; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) is essential for the de novo synthesis of thymidylate, a precursor of DNA. Previous studies have shown that the cellular level of this protein is regulated at both the transcriptional and posttranscriptional levels. The regulation of human TS mRNA translation was studied in vitro with a rabbit reticulocyte lysate system. The addition of purified human recombinant TS protein to in vitro translation reactions inhibited translation of TS mRNA. This inhibition was specific in that recombinant TS protein had no effect on the in vitro translation of mRNA for human chromogranin A, human folate receptor, preplacental lactogen, or total yeast RNA. The inclusion of dUMP, 5-fluoro-dUMP, or 5,10-methylene-tetrahydrofolate in in vitro translation reactions completely relieved the inhibition of TS mRNA translation by TS protein. Gel retardation assays confirmed a specific interaction between TS protein and its corresponding mRNA but not with unrelated mRNAs, including human placenta, human β-actin, and yeast tRNA. These studies suggest that translation of TS mRNA is controlled by its own protein end product, TS, in an autoregulatory manner.

Original languageEnglish (US)
Pages (from-to)8977-8981
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number20
StatePublished - Oct 15 1991
Externally publishedYes

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Thymidylate Synthase
Protein Biosynthesis
Homeostasis
Messenger RNA
Recombinant Proteins
Proteins
Yeasts
Reticulocytes
Electrophoretic Mobility Shift Assay
Transfer RNA
Folic Acid
Placenta
Actins
RNA
Rabbits
In Vitro Techniques
DNA

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase. / Chu, Edward; Koeller, David; Casey, John L.; Drake, James C.; Chabner, Bruce A.; Elwood, Patrick C.; Zinn, Sydelle; Allegra, Carmen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 88, No. 20, 15.10.1991, p. 8977-8981.

Research output: Contribution to journalArticle

Chu, Edward ; Koeller, David ; Casey, John L. ; Drake, James C. ; Chabner, Bruce A. ; Elwood, Patrick C. ; Zinn, Sydelle ; Allegra, Carmen J. / Autoregulation of human thymidylate synthase messenger RNA translation by thymidylate synthase. In: Proceedings of the National Academy of Sciences of the United States of America. 1991 ; Vol. 88, No. 20. pp. 8977-8981.
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