The rTS gene codes for a naturally occurring antisense RNA to thymidylate synthase (TS) mRNA and two proteins (rTSalpha and rTSbeta (also known as ENOSF1)). The role of the major protein product of rTS, ENOSF1 has been linked to alterations in TS protein expression, but the precise function of ENOSF1 is unknown. Expression of rTS is associated with growth arrest in cell culture, but its overexpression has been noted in cells resistant to anticancer drugs such as 5-fluorouracil and methotrexate. Studies have shown that increased expression of ENOSF1 is associated with the decrease in TS protein expression due to production of novel, diffusible signal molecules.