Levin H L, Weaver D C, Boeke J D
Department of Molecular Biology and Genetics, Johns Hopkins School of Medicine, Baltimore, MD 21205.
EMBO J. 1993 Dec;12(12):4885-95. doi: 10.1002/j.1460-2075.1993.tb06178.x.
In sharp contrast to the single ORF of the Schizosaccharomyces pombe retrotransposon Tf1, retroviruses and most retrotransposons employ two different ORFs to separately encode the Gag and Pol proteins. The different ORFs are thought to allow for overexpression of the Gag protein relative to Pol protein presumed necessary for the assembly of functional retrovirus particles and virus-like particles (VLPs). The results of in vivo experiments designed to detect the transposition of Tf1 show that Tf1 is indeed active and can insert itself into the host genome via a true retrotransposition process. Thus, a paradox emerged between the lack of any obvious means of overexpressing Tf1 Gag protein and the demonstrated functionality of the element. Epitope tagging experiments described here confirm that the Tf1 large ORF is intact and that there is no translational or transcriptional mechanism used to overexpress the Tf1 Gag protein. In addition, we used sucrose gradients and antisera specific for Tf1 capsid (CA) and integrase (IN) to show that the Tf1 proteins do assemble into uniform populations of macromolecular particles that also cosediment with Tf1 reverse transcription products. This evidence suggests that Tf1 proteins form VLPs without using the previously described mechanisms that retroviruses and retrotransposons require to overexpress Gag proteins.
与粟酒裂殖酵母逆转录转座子Tf1的单一开放阅读框形成鲜明对比的是,逆转录病毒和大多数逆转录转座子采用两个不同的开放阅读框来分别编码Gag和Pol蛋白。不同的开放阅读框被认为允许Gag蛋白相对于Pol蛋白过度表达,而Pol蛋白被认为是组装功能性逆转录病毒颗粒和病毒样颗粒(VLP)所必需的。旨在检测Tf1转座的体内实验结果表明,Tf1确实具有活性,并且可以通过真正的逆转录转座过程将自身插入宿主基因组。因此,在缺乏任何明显的过度表达Tf1 Gag蛋白的手段与该元件已证明的功能之间出现了矛盾。本文所述的表位标签实验证实,Tf1的大开放阅读框是完整的,并且不存在用于过度表达Tf1 Gag蛋白的翻译或转录机制。此外,我们使用蔗糖梯度以及针对Tf1衣壳(CA)和整合酶(IN)的抗血清,以表明Tf1蛋白确实组装成了均匀的大分子颗粒群体,这些颗粒也与Tf1逆转录产物一起沉降。这一证据表明,Tf1蛋白形成VLP时并未使用逆转录病毒和逆转录转座子过度表达Gag蛋白所需的先前描述的机制。