Thymidylate synthase mRNA (TYMS mRNA) (TYMS mRNA)

Thymidylate synthase mRNA (TYMS mRNA) is the messenger RNA transcript that encodes the thymidylate synthase enzyme, a critical component in the de novo synthesis of 2-deoxythymidine-5-monophosphate (dTMP) required for DNA replication and repair (Chu et al., 1991). This mRNA is biologically unique due to its involvement in a translational autoregulatory loop, where the thymidylate synthase protein binds to its own mRNA at specific sites to repress further translation (Chu et al., 1991; Tai et al., 2004). In many cancers, including colorectal and gastric malignancies, the overexpression of TYMS mRNA is a primary driver of resistance to fluoropyrimidine-based chemotherapies like 5-fluorouracil (Popat et al., 2004). When these drugs inhibit the TS protein, the autoregulatory loop is disrupted, leading to a compensatory surge in TYMS mRNA translation and a subsequent increase in protein levels that bypasses the drug's effect (Peters et al., 2002). Consequently, TYMS mRNA has emerged as a direct therapeutic target for antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) designed to degrade the transcript and prevent this rebound resistance (Lin et al., 2001). By targeting the mRNA directly, these strategies aim to sensitize tumor cells to conventional antifolates and improve clinical outcomes in patients with high TYMS expression.

Other names

TS mRNAThymidylate synthetase mRNATYMS transcriptThymidylate synthase messenger RNA

Antisense-mediated mRNA degradation, RNA interference (RNAi), and disruption of the translational autoregulatory feedback loop.