Intronless human dihydrofolate reductase genes are derived from processed RNA molecules.
Intronless human dihydrofolate reductase genes are derived from processed RNA molecules.
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无内含子人二氢叶酸还原酶基因源自加工的RNA分子。
DOI：
10.1073/pnas.79.23.7435
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发表时间：
1982
影响因子：
11.1
通讯作者：
A. Nienhuis
中科院分区：
文献类型：
--
作者：
M. Chen;T. Shimada;A. Moulton;M. Harrison;A. Nienhuis
从两个人DNA克隆文库中分离出三组含有二氢叶酸还原酶（DHFR；四氢叶酸脱氢酶；5,6,7,8-四氢叶酸：NADP+氧化还原酶，EC 1.5.1.3）编码序列的重组噬菌体。一种重组体 (lambda hDHFR-1) 包含三个编码人 DHFR COOH 末端部分的外显子。另外两个人类 DHFR 基因（hDHFR-psi 1 和 hDHRF-psi 2）缺乏内含子。 hDHFR-psi 2 含有多个同相终止密码子，与正常人 DHFR 编码序列仅 93% 同源，而 hDHFR-psi 1 具有开放阅读框，与正常 DHFR 基因的编码序列几乎相同。每个无内含子基因和正常DHFR基因之间的DNA序列同源性区域延伸超出编码序列末端2.9kb。在该同源序列的 3' 端，每个无内含子基因都有一个富含 A 的区域。内含子的缺乏和 3'A 丰富区的存在表明 hDHFR-psi 1 和 hDHFR-psi 2 源自加工的 RNA 分子。一段短 DNA 序列，位于 lambda hDHFR-psi 2 中 ATG 起始密码子 5' 处的 60 个核苷酸，在 3' A 富集区之后立即直接重复；这种末端同向重复序列也位于整合的原逆转录病毒和转座DNA元件的侧翼，并被认为是插入DNA序列的标志。
Three groups of recombinant bacteriophage containing coding sequences for dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3) were isolated from two human DNA clone libraries. One recombinant (lambda hDHFR-1) contains three exons that encode the COOH-terminal portion of human DHFR. The other two human DHFR genes (hDHFR-psi 1 and hDHRF-psi 2) lack introns. hDHFR-psi 2 contains several in-phase termination codons and is only 93% homologous to the normal human DHFR coding sequences, whereas hDHFR-psi 1 has an open reading frame and is virtually identical to the coding sequence of the normal DHFR gene. The region of DNA sequence homology between each intronless gene and the normal DHFR gene extends 2.9 kilobases beyond the end of the coding sequences. At the 3' end of this homologous sequence, each intronless gene has an A-rich tract. The lack of introns and the presence of the 3' A-rich tract suggest that hDHFR-psi 1 and hDHFR-psi 2 were derived from processed RNA molecules. A short DNA sequence, 60 nucleotides 5' to the ATG start codon in lambda hDHFR-psi 2, is directly repeated immediately after the 3' A-rich tract; such terminal direct repeats also flank integrated proretroviruses and transposable DNA elements and are thought to be the hallmark of inserted DNA sequences.