HUMAN THYMIDYLATE SYNTHASE ANTISENSE RNA

胸苷酸合成酶（TS）是结直肠癌化疗的重要靶点 癌症和其他实体瘤。5-氟尿嘧啶， 转移性结直肠癌的治疗具有抑制TS作为主要的 代谢后作用位点转化为相应的脱氧核苷酸。 因为它是药物作用的靶点和关键酶 TS基因参与DNA生物合成，其调控已被 实质性调查的主题。 TS基因表达的调控 已经证明人和鼠细胞是转录后的 被人 现在已经确定人类细胞含有RNA 与人胸苷酸的部分互补的物种 合成酶基因和mRNA。 至少有两种不同类型的 反义RNA。 对应于TS反义RNA（3 'rTS）的cDNA克隆 RNA）已经获得并表征。3 'rTS RNA被多聚腺苷酸化， 明显剪接并与3 '非编码区，外显子7和a重叠， 人TS基因内含子6的一部分。 这是第一 展示了与人类基因重叠的反义RNA， 多聚腺苷酸化和明显的剪接。 建议TS 反义RNA被更充分地表征，它们的身份是发挥作用的。 在TS基因表达中的作用。 可能的相互作用 将研究这些有义和反义基因转录物。 也是 提出，如果TS反义RNA在TS基因表达中的作用是 发现，与细胞暴露于TS抑制剂的相关性是 调查，以确定是否可以利用这一点来改善 细胞毒

Thymidylate synthase (TS) is a key target for chemotherapy of colorectal cancer and other solid tumors. 5-fluorouracil, the drug of choice for treatment of metastatic colorectal cancer has inhibition of TS as a major site of action after metabolism to the corresponding deoxynucleotide. Because of its role as a target of drug action and as a key enzyme involved in DNA biosynthesis, the TS gene and its regulation have been topics of substantial investigation. Regulation of TS gene expression in human and murine cells has been demonstrated to be post-transcriptional by others. It has now been determined that human cells contain RNA species which are complementary to portions of the human thymidylate synthase gene and mRNA. There are at least two distinct types of antisense RNAs. A cDNA clone corresponding to a TS antisense RNA (3'rTS RNA) has been obtained and characterized. 3'rTS RNA is polyadenylated, apparently spliced and overlaps with the 3'noncoding region, exon 7 and a portion of intron 6 of the human TS gene. This is the first demonstration of an antisense RNA which overlaps a human gene and is both polyadenylated and apparently spliced. It is proposed that the TS antisense RNAs be more fully characterized and their identity as playing a role in TS gene expression be determined. The possible interaction of these sense and antisense gene transcripts will be studied. It is also proposed that if a role of TS antisense RNAs in TS gene expression is found, the relevance to exposure of cells to TS inhibitors be investigated to determine if this can be exploited to improve cytotoxicity.