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Research Paper
A Novel Function for the rTS gene
Bruce J. Dolnick, Norman J. Angelino, Ree Dolnick and Janice R. Sufrin
volume 2 | issue 4
july/august 2003Pages: 364-369
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The rTS gene codes for a naturally occurring antisense RNA to thymidylate synthase (TS) mRNA and two proteins (rTSa and rTSb). The role of the major protein product of rTS, rTb has been linked to alterations in TS protein expression, but the precise function of rTSb is unknown. In this report we demonstrate that increased expression of rTSb is associated with the decrease in TS protein expression due to production of novel, diffusible signal molecules. These signal molecules are produced more abundantly when rTSb amounts are elevated. This hypothesis is supported by the demonstration that the rTSb-overproducing cell line H630-1 can down-regulate TS protein in other cells without direct cellular contact. These cells are shown to secrete significant amounts of lipophilic metabolites derived from methionine, in contrast to cells that do not overproduce rTSb. In support of the hypothesis that rTSb is essential for the generation of these compounds, we demonstrate that rTSb can catalyze the transfer of the carboxyl carbon of methionine from S-adenosylmethionine to a lipophilic acceptor molecule in vitro. We propose rTS is involved in regulation of TS through a novel methionine-based signaling pathway.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.