Translational profiling of B cells infected with the Epstein-Barr virus reveals 5′ leader ribosome recruitment through upstream open reading frames
Translational profiling of B cells infected with the Epstein-Barr virus reveals 5′ leader ribosome recruitment through upstream open reading frames
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DOI：
10.1093/nar/gky129
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发表时间：
2018-04-06
影响因子：
14.9
通讯作者：
Delecluse, Henri-Jacques
中科院分区：
文献类型：
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作者：
Bencun, Maja;Klinke, Olaf;Delecluse, Henri-Jacques
EB病毒（EBV）基因组编码数百个转录本。我们已经使用核糖体分析来表征感染细胞中的病毒翻译并绘制新的翻译起始位点。我们在这里表明，EBV转录翻译的效率高度可变，由于可变的转录和翻译速率，可变的核糖体募集到前导区和覆盖的单核糖体与多核糖体。有些转录本几乎不翻译，其他主要携带单体，显示核糖体积累在前导区，最有可能代表非编码RNA。一个类似的过程是可见的裂解基因的子集，包括关键的反式激活因子BZLF1和BRLF1在细胞感染弱复制型EBV株。这表明，核糖体陷阱，特别是在前导区，代表了一个新的检查点裂解复制的镇压。在编码转录本上游共发现25个5'前导核糖体捕获的上游开放阅读框（uORF），其中6个位于许多潜在转录本共有的前导区。这些uORF抑制病毒的翻译，并可能在调节EBV的翻译中发挥重要作用。
The Epstein-Barr virus (EBV) genome encodes several hundred transcripts. We have used ribosome profiling to characterize viral translation in infected cells and map new translation initiation sites. We show here that EBV transcripts are translated with highly variable efficiency, owing to variable transcription and translation rates, variable ribosome recruitment to the leader region and coverage by mono-somes versus polysomes. Some transcripts were hardly translated, others mainly carried monosomes, showed ribosome accumulation in leader regions and most likely represent non-coding RNAs. A similar process was visible for a subset of lytic genes including the key transactivators BZLF1 and BRLF1 in cells infected with weakly replicating EBV strains. This suggests that ribosome trapping, particularly in the leader region, represents a new checkpoint for the repression of lytic replication. We could identify 25 upstream open reading frames (uORFs) located upstream of coding transcripts that displayed 5' leader ribosome trapping, six of which were located in the leader region shared by many latent transcripts. These uORFs repressed viral translation and are likely to play an important role in the regulation of EBV translation.