HUMAN THYMIDYLATE SYNTHASE ANTISENSE RNA

胸苷合成酶(TS)是结直肠癌化疗的关键靶点 癌症和其他实体肿瘤。5-氟尿嘧啶，治疗癌症的首选药物 转移性结直肠癌的治疗以抑制TS为主 作用部位代谢后为相应的脱氧核苷酸。 因为它是药物作用的靶点和关键酶 参与DNA生物合成的TS基因及其调控已被 实质性调查的主题。水稻TS基因表达的调控 人类和小鼠细胞已被证明是转录后 被其他人。现在已经确定人类细胞含有核糖核酸 与人类胸腺嘧啶核苷部分互补的物种 合酶基因和mRNA。至少有两种不同类型的 反义RNA。一个与TS反义RNA(3‘RTS)相对应的cDNA克隆 RNA)，并对其进行了鉴定。3‘RTS RNA是多腺化的， 与3‘非编码区、外显子7和a 人类TS基因内含子6的一部分。这是第一次 一种与人类基因重叠的反义RNA的演示 多聚腺苷和明显的剪接。有人建议，交通运输系统 反义RNA的特征更加充分，它们的身份也在发挥作用 在TS基因表达中的作用被确定。可能存在的相互作用 这些正义和反义基因转录本将被研究。它也是 提出如果TS反义RNA在TS基因表达中的作用是 发现，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进 细胞毒性。

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.