Frameshifting in Alphaviruses: A Diversity of 3′ Stimulatory Structures
Frameshifting in Alphaviruses: A Diversity of 3′ Stimulatory Structures
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DOI：
10.1016/j.jmb.2010.01.044
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发表时间：
2010-03-26
影响因子：
5.6
通讯作者：
Atkins, John F.
中科院分区：
文献类型：
--
作者：
Chung, Betty Y. -W.;Firth, Andrew E.;Atkins, John F.
程序化的核糖体移码允许从相同的RNA合成交替的、N-末端一致的、C-末端不同的蛋白质。许多病毒利用移码来优化紧凑基因组的编码潜力，以规避宿主细胞每个mRNA一个功能蛋白的规范规则，或以固定比例表达替代蛋白。程序化移码也被用于解码少量的细胞基因。最近，在编码甲病毒6 K蛋白的序列内的保守U_UUU_UUA基序处发现了特异性核糖体1移码。在这种情况下，移码导致合成额外的蛋白质，称为TF（transframe）。这种新的移码是不寻常的，因为1框ORF非常短，完全嵌入编码重叠多蛋白的序列中。目前的工作表明，有显着的多样性，在3'序列，是功能上重要的有效移码在U_UUU_UUA基序。虽然许多甲病毒物种利用3' RNA结构，如发夹或假结，但一些物种（如Semliki Forest病毒）显然缺乏任何mRNA内刺激结构，但仅与移位位点3'相邻的20 nt就刺激高达10%的移码。分析，实验和生物信息学，显着扩大了已知的剧目1移码刺激在哺乳动物和昆虫系统。(C)2010爱思唯尔有限公司版权所有。
Programmed ribosomal frameshiffing allows the synthesis of alternative, N-terminally coincident, C-terminally distinct proteins from the same RNA. Many viruses utilize frameshifting to optimize the coding potential of compact genomes, to circumvent the host cell's canonical rule of one functional protein per mRNA, or to express alternative proteins in a fixed ratio. Programmed frameshifting is also used in the decoding of a small number of cellular genes. Recently, specific ribosomal 1 frameshifting was discovered at a conserved U_UUU_UUA motif within the sequence encoding the alphavirus 6K protein. In this case, frameshifting results in the synthesis of an additional protein, termed TF (Trans Frame). This new case of frameshifting is unusual in that the 1 frame ORF is very short and completely embedded within the sequence encoding the overlapping polyprotein. The present work shows that there is remarkable diversity in the 3' sequences that are functionally important for efficient frameshifting at the U_UUU_UUA motif. While many alphavirus species utilize a 3' RNA structure such as a hairpin or pseudoknot, some species (such as Semliki Forest virus) apparently lack any intra-mRNA stimulatory structure, yet just 20 nt 3'-adjacent to the shift site stimulates up to 10% frameshifting. The analysis, both experimental and bioinformatic, significantly expands the known repertoire of 1 frameshifting stimulators in mammalian and insect systems. (C) 2010 Elsevier Ltd. All rights reserved.