Michaeli T, Prives C
Nucleic Acids Res. 1987 Feb 25;15(4):1579-94. doi: 10.1093/nar/15.4.1579.
SV40 DNA form I is expressed efficiently after its injection into the nuclei of Xenopus laevis oocytes, resulting in the synthesis of RNA and protein products of both viral late and early transcription units. However it was observed that injection of SV40 genes cloned into pBR322 or related plasmids yielded vastly reduced quantities of viral DNA and proteins. If SV40 DNA was cleaved from the plasmid, and then recircularized prior to microinjection, viral expression was regained. The inhibition by plasmid DNA was not confined to an effect in cis because coinjection of circular pBR322 DNA along with SV40 DNA, as separate entities, also blocked viral RNA and protein synthesis. As circular but not linear pBR322 DNA was actively transcribed by polymerase II in oocytes, even in the presence of SV40 DNA, it is likely that pBR322 competes for transcription factors required for viral gene expression. Injection of pBR322 as early as two hours after injection of SV40 DNA into the oocyte nucleus did not inhibit SV40 RNA synthesis, indicating that once initiated, SV40 transcription is stable and insensitive to the competition by plasmid DNA. A plasmid vector was developed that allows expression of SV40 DNA in Xenopus laevis oocytes.
SV40 DNA 形式 I 注射到非洲爪蟾卵母细胞核后能高效表达,导致病毒晚期和早期转录单元的 RNA 和蛋白质产物合成。然而,观察到将克隆到 pBR322 或相关质粒中的 SV40 基因注射后,病毒 DNA 和蛋白质的产量大幅降低。如果在显微注射前将 SV40 DNA 从质粒上切割下来,然后再环化,病毒表达就能恢复。质粒 DNA 的抑制作用并不局限于顺式效应,因为将环状 pBR322 DNA 与 SV40 DNA 作为单独的实体共同注射,也会阻断病毒 RNA 和蛋白质的合成。由于环状而非线性的 pBR322 DNA 在卵母细胞中能被聚合酶 II 积极转录,即使存在 SV40 DNA,pBR322 很可能会竞争病毒基因表达所需的转录因子。早在将 SV40 DNA 注射到卵母细胞核两小时后注射 pBR322 并不抑制 SV40 RNA 的合成,这表明一旦启动,SV40 转录是稳定的,对质粒 DNA 的竞争不敏感。开发了一种质粒载体,可使 SV40 DNA 在非洲爪蟾卵母细胞中表达。