POINT MUTANTS OF MOLONEY MURINE LEUKEMIA-VIRUS THAT FAIL TO PACKAGE VIRAL-RNA - EVIDENCE FOR SPECIFIC RNA RECOGNITION BY A ZINC FINGER-LIKE PROTEIN-SEQUENCE
POINT MUTANTS OF MOLONEY MURINE LEUKEMIA-VIRUS THAT FAIL TO PACKAGE VIRAL-RNA - EVIDENCE FOR SPECIFIC RNA RECOGNITION BY A ZINC FINGER-LIKE PROTEIN-SEQUENCE
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DOI：
10.1073/pnas.85.22.8420
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发表时间：
1988-11-01
影响因子：
11.1
通讯作者：
REIN, A
中科院分区：
文献类型：
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作者：
GORELICK, RJ;HENDERSON, LE;REIN, A
所有逆转录病毒都编码一种核酸结合蛋白或核衣壳蛋白，据信该蛋白与病毒体中的RNA相关。此外，所有逆转录病毒核衣壳蛋白含有序列Cys-Xaa 2-Cys-Xaa 4-His-Xaa 4-Cys的一个或两个拷贝。该序列的保守性表明它对病毒复制很重要，并且它与真核转录因子中发现的“锌指”序列的相似性提高了它在逆转录病毒组装过程中识别病毒RNA中特定序列的可能性。我们使用三聚氰胺定向诱变在莫洛尼鼠白血病病毒的核衣壳蛋白编码区产生一系列突变。这些突变将单个氨基酸（包括每个半胱氨酸）改变为丝氨酸。突变病毒基因组指导病毒颗粒的合成;这些颗粒缺乏可检测的病毒RNA，但确实含有显著水平的细胞RNA。因此，这些突变似乎破坏了病毒蛋白在病毒组装过程中特异性包装病毒RNA的能力。我们建议，在逆转录病毒核衣壳蛋白的保守序列的功能在RNA序列识别，并建议它进化相关的锌指，识别特定的双链DNA序列。
All retroviruses encode a nucleic acid-bindng or nucleocapsid protein that is believed to be associated with RNA in the virion. Further, all retroviral nucleocapsid proteins contain either one or two copies of the sequence Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. The conservation of this sequence suggested that it is important for virus replication, and its resemblance to the "zinc-finger" sequences found in eukaryotic transcription factors raised the possibility that it recognizes specific sequences in viral RNA during retrovirus assembly. We used oligonucleotide-directed mutagenesis to generate a series of mutations in the nucleocapsid protein-coding region of Moloney murine leukemia virus. These mutations changed single amino acids, including each of the cysteines, to serine. The mutant viral genomes direct the synthesis of virus particles; these particles lack detectable viral RNA but do contain significant levels of cellular RNAs. Thus it appears that the mutations have destroyed the ability of the viral proteins to specifically package viral RNA during virus assembly. We propose that the conserved sequence in retroviral nucleocapsid proteins functions in RNA sequence recognition and suggest that it evolutionarily related to the zinc fingers that recognize specific sequences in double-stranded DNA.