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莫洛尼鼠白血病病毒的逆转录酶与真核释放因子1结合,以调节翻译终止的抑制作用。

Reverse transcriptase of Moloney murine leukemia virus binds to eukaryotic release factor 1 to modulate suppression of translational termination.

作者信息

Orlova Marianna, Yueh Andrew, Leung Juliana, Goff Stephen P

机构信息

Department of Biochemistry and Molecular Biophysics, Integrated Program in Cell and Molecular Biology, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

出版信息

Cell. 2003 Oct 31;115(3):319-31. doi: 10.1016/s0092-8674(03)00805-5.

Abstract

The pol (for polymerase) gene of the murine leukemia viruses (MuLVs) is expressed in the form of a large Gag-Pol precursor protein by the suppression of translational termination, or enhanced readthrough, of a UAG stop codon at the end of gag. A search for cellular proteins that interact with the reverse transcriptase of Moloney MuLV resulted in the identification of eRF1, the eukaryotic translation release factor 1. The proteins bound strongly in vitro, and the overexpression of eRF1 resulted in the RT-dependent incorporation of the protein into assembling virion particles. The overexpression of RT in trans enhanced the translational readthrough of a reporter construct containing the Gag-Pol boundary region. Noninteracting mutants of RT failed to synthesize adequate levels of Gag-Pol and could not replicate. These results suggest that RT enhances suppression of termination and that the interaction of RT with eRF1 is required for an appropriate level of translational readthrough.

摘要

鼠白血病病毒(MuLVs)的pol(聚合酶)基因通过抑制gag末端UAG终止密码子的翻译终止或增强通读,以大Gag-Pol前体蛋白的形式表达。对与莫洛尼MuLV逆转录酶相互作用的细胞蛋白进行搜索,结果鉴定出真核翻译释放因子1(eRF1)。这些蛋白在体外强烈结合,eRF1的过表达导致该蛋白依赖逆转录酶(RT)整合到组装中的病毒粒子中。反式过表达RT增强了含有Gag-Pol边界区域的报告构建体的翻译通读。RT的非相互作用突变体无法合成足够水平的Gag-Pol,且不能复制。这些结果表明,RT增强了终止抑制,并且RT与eRF1的相互作用是适当水平的翻译通读所必需的。

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