The 5' leader of the mRNA encoding the marek's disease virus serotype 1 pp14 protein contains an intronic internal ribosome entry site with allosteric properties.

The 5' leader of the mRNA encoding the marek's disease virus serotype 1 pp14 protein contains an intronic internal ribosome entry site with allosteric properties.
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编码马立克氏病病毒血清型 1 pp14 蛋白的 mRNA 5 前导序列包含具有变构特性的内含子内部核糖体进入位点。

DOI:
10.1128/jvi.01010-09
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发表时间:
2009
影响因子:
5.4
通讯作者:
Tahiri-Alaoui A
Tahiri-Alaoui A
中科院分区:
医学2区
文献类型:
--
作者:
Tahiri-Alaoui A

文献摘要

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我们证明了在编码马立克氏病病毒(MDV)血清1型pp 14和RLORF 9蛋白的双顺反子mRNA变体的5′前导序列(命名为5L)中存在功能性内部核糖体进入位点(IRES)。成熟的双顺反子mRNAs作为一个1.8kb的即刻早期基因家族,由于选择性剪接或启动子的使用,具有可变的5′前导序列。因此,mRNA中5L IRES的存在或不存在决定了pp 14翻译的模式,并导致产生两种N-末端序列不同的pp 14同种型。实时逆转录-定量PCR表明,在MDV感染和转化的细胞中,具有5L IRES的mRNA变体的丰度是缺乏5L IRES的mRNA变体的2至3倍。1.8-kb转录物家族所有成员的共同特征是存在顺反子间IRES,我们先前已经证明该IRES控制第二开放阅读框的翻译(即,RLORF 9)。对位于相同双顺反子报告mRNA中的两个IRES的研究揭示了翻译效率的功能协同作用。与蛋白质中的变构模型类似,我们提出IRES变构来描述这种新现象。我们的研究结果的功能意义进行了讨论,在宿主病毒的相互作用和翻译控制。
We demonstrate the presence of a functional internal ribosome entry site (IRES) within the 5′ leader (designated 5L) from a variant of bicistronic mRNAs that encode the pp14 and RLORF9 proteins from Marek's disease virus (MDV) serotype 1. Transcribed as a 1.8-kb family of immediate-early genes, the mature bicistronic mRNAs have variable 5′ leader sequences due to alternative splicing or promoter usage. Consequently, the presence or absence of the 5L IRES in the mRNA dictates the mode of pp14 translation and leads to the production of two pp14 isoforms that differ in their N-terminal sequences. Real-time reverse transcription-quantitative PCR indicates that the mRNA variants with the 5L IRES is two to three times more abundant in MDV-infected and transformed cells than the mRNA variants lacking the 5L IRES. A common feature to all members of the 1.8-kb family of transcripts is the presence of an intercistronic IRES that we have previously shown to control the translation of the second open reading frame (i.e., RLORF9). Investigation of the two IRESs residing in the same bicistronic reporter mRNA revealed functional synergism for translation efficiency. In analogy with allosteric models in proteins, we propose IRES allostery to describe such a novel phenomenon. The functional implications of our findings are discussed in relation to host-virus interactions and translational control.