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Alternate splicing of the rTS gene product and its overexpression in a 5-fluorouracil-resistant cell line.

rTS is a gene with convergent and overlapping transcription relative to thymidylate synthase (TS). Screening of a cDNA library has identified a second rTS RNA (rTSbeta) which is related to a previously described rTS RNA (rTSalpha). rTSbeta differs from rTSalpha by the insertion of an extra 116 nucleotides after base 128 of rTSalpha and an altered 3'-noncoding region such that rTSbeta RNA is not complementary to TS mRNA. rTSalpha and rTSbeta RNAs have open reading frames predicted to encode proteins of 361 and 416 amino acids, respectively. Antibody to rTSbeta protein detects two proteins of the predicted molecular weight in the H630 colon tumor cell line. rTSbeta is overexpressed 40-70-fold in a 5-fluorouracil-resistant H630 subline compared with 7-8-fold for TS and rTSalpha.