THE 5'-ENDS OF HANTAAN VIRUS (BUNYAVIRIDAE) RNAS SUGGEST A PRIME-AND-REALIGN MECHANISM FOR THE INITIATION OF RNA-SYNTHESIS
THE 5'-ENDS OF HANTAAN VIRUS (BUNYAVIRIDAE) RNAS SUGGEST A PRIME-AND-REALIGN MECHANISM FOR THE INITIATION OF RNA-SYNTHESIS
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DOI：
10.1128/jvi.69.9.5754-5762.1995
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发表时间：
1995-09-01
影响因子：
5.4
通讯作者：
KOLAKOFSKY, D
中科院分区：
文献类型：
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作者：
GARCIN, D;LEZZI, M;KOLAKOFSKY, D
我们检查了汉滩病毒（HTN）基因组和mRNA的5'端，以了解这些链的起始方式。与迄今为止描述的布尼亚病毒科的所有成员一样，HTN mRNA含有5'末端延伸，其在长度和序列上都是异质的，大概是因为HTN也“帽抓取”宿主mRNA以启动病毒mRNA。然而，出乎意料的是，几乎所有的mRNA在位置-1处含有G残基，并且大部分在末端也恰好缺少三个UAG重复中的一个。另一方面，基因组以位置+1的U残基开始，但在这里仅发现5'单磷酸，表明这些链可能不是以该位置的UTP开始的。总之，这些不寻常的发现表明链起始的引发-再对齐机制，其中mRNA是用G-终止的宿主细胞引物和具有GTP的基因组起始的，而不是在基因组模板的3'末端，而是在内部。（与模板C在位置+3处相对），并且在延伸一个或几个核苷酸后，新生链凭借末端序列重复向后重新排列，在进行性伸长发生之前。对于基因组起始，假设核酸内切酶（可能参与帽抢夺的核酸内切酶）去除基因组的5'末端延伸，在位置+1处留下5' pU。
We examined the 5' ends of Hantaan virus (HTN) genomes and mRNAs to gain insight into the manner in which these chains were initiated. Like those of all members of the family Bunyaviridae described so far, the HTN mRNAs contained 5' terminal extensions that were heterogeneous in both length and sequence, presumably because HTN also ''cap snatches'' host mRNAs to initiate the viral mRNAs. Unexpectedly however, almost ah of the mRNAs contained a G residue at position -1, and a large fraction also lacked precisely one of the three UAG repeats at the termini. The genomes, on the other hand, commenced with a U residue at position +1, but only 5' monophosphates were found here, indicating that these chains may not have initiated with UTP at this position. Taken together, these unusual findings suggest a prime-and-realign mechanism of chain initiation in which mRNAs are initiated with a G-terminated host cell primer and genomes with GTP, not at the 3' end of the genome template but internally (opposite the template C at position +3), and after extension by one or a few nucleotides, the nascent chain realigns backwards by virtue of the terminal sequence repeats, before processive elongation takes place. For genome initiation, an endonuclease, perhaps that involved in cap snatching, is postulated to remove the 5' terminal extension of the genome, leaving the 5' pU at position +1.