Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome
Ribosomal frameshifting into an overlapping gene in the 2B-encoding region of the cardiovirus genome
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DOI：
10.1073/pnas.1102932108
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发表时间：
2011-11-15
影响因子：
11.1
通讯作者：
Atkins, John F.
中科院分区：
文献类型：
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作者：
Loughran, Gary;Firth, Andrew E.;Atkins, John F.
心脏病毒属（小核糖核酸病毒科）目前包括脑心肌炎病毒（EMCV）和theilvirus。心脏病毒有一个正意义的单链RNA基因组，编码一个大的多蛋白（L-1ABCD-2ABC-3ABCD），该多蛋白被切割后产生大约12种成熟蛋白。我们报道了一个保守的ORF，它在+2阅读框中与EMCV的2b编码序列重叠。ORF在保守的GGUUUUY基序上通过核糖体移框，与2B的n端11-12个氨基酸进行128-129个氨基酸的跨框融合（2B*）。敲除2B*表达的突变导致小斑块表型。奇怪的是，尽管它们的病毒序列在这个基因组位置的+2框架中缺乏一个长ORF，但它们在2A-2B连接处的下游保持一个保守的GGUUUUU基序，并且在多蛋白框架同义位点的高度定位的保守峰值表明它们的病毒在这里也利用了帧移位，尽管是一个非常短的+2框架ORF。与以前的编程-1移帧不同，这里的移帧是由病毒感染调节的，因此表明这些病毒的移帧具有新的调节作用。
The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128-129 amino acid transframe fusion (2B*) with the N-terminal 11-12 amino acids of 2B, via ribosomal frameshifting at a conserved GGUUUUY motif. Mutations that knock out expression of 2B* result in a small-plaque phenotype. Curiously, although theilovirus sequences lack a long ORF in the +2 frame at this genomic location, they maintain a conserved GGUUUUU motif just downstream of the 2A-2B junction, and a highly localized peak in conservation at polyprotein-frame synonymous sites suggests that theiloviruses also utilize frameshifting here, albeit into a very short +2-frame ORF. Unlike previous cases of programmed -1 frameshifting, here frameshifting is modulated by virus infection, thus suggesting a novel regulatory role for frameshifting in these viruses.