Ribosome "Skipping": "Stop-Carry On" or "StopGo" Translation
Ribosome "Skipping": "Stop-Carry On" or "StopGo" Translation
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DOI：
10.1007/978-0-387-89382-2_5
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Ryan, Martin D.
中科院分区：
文献类型：
--
作者：
Brown, Jeremy D.;Ryan, Martin D.
2A和2A样“CHYSEL”序列（“2A”）是指定核糖体“跳过”（也称为“停止继续”或“停止去”翻译）的寡肽。在这种形式的重编码事件中，跳过了特定肽键（2A的c端甘氨酸和下游肽的n端脯氨酸之间）的合成。我们提出了一个模型，其中新生的2A寡肽与核糖体的出口通道相互作用，以停止或暂停进程。我们认为这种相互作用也抑制了肽键固结的机制，并且新生蛋白被释放因子I和3释放（以停止密码子独立的方式）。然后翻译可以在脯氨酸密码子处“伪重新启动”，使得形成两个离散的翻译产物。虽然首先在哺乳动物正链RNA病毒（小核糖核酸病毒）中发现，但在许多昆虫正链RNA病毒以及哺乳动物、昆虫和甲壳类动物双链RNA病毒中也发现了2As。细胞蛋白的生物发生也可能受到2As的控制：在锥虫和紫海胆基因组的非ltr逆转录转座子中也发现了这样的序列。2A似乎形成了编码CATERPILLER蛋白（参与先天免疫反应）的海胆基因开放阅读框的n端区域。事实上，大约50%的基因都是从2A开始的。因此，这种形式的重新编码似乎在控制病原体和先天免疫系统中的蛋白质生物发生中起着重要作用。
2A and 2A-like "CHYSEL" sequences ("2As") are oligopeptides that specify ribosome "skipping" (also referred to as "Stop-Carry On" or "StopGo" translation). In this form of recoding event, the synthesis of a specific peptide bond (between the C-terminal glycine of 2A and the N-terminal proline of the downstream peptide) is skipped. We have proposed a model in which the nascent 2A oligopeptide interacts with the exit tunnel of the ribosome to stall, or pause, processivity. We propose this interaction also inhibits the mechanism of peptide bond fort-nation and that the nascent protein is released (in a stop codon-independent manner) by release factors I and 3. Translation may then "pseudo-reinitiate" at the proline codon such that two discrete translation products are formed. Although first identified within positive-stranded mammalian RNA viruses (picornaviruses), 2As are also found in a wide range of insect positive-stranded RNA viruses plus mammalian, insect and crustacean double-stranded RNA viruses. Cellular protein biogenesis may also be controlled by 2As: such sequences are also found within non-LTR retrotransposons in the genomes of trypanosomes and the purple sea urchin. 2A appears to form the N-terminal region of open reading frames of sea urchin genes encoding CATERPILLER proteins (involved in the innate immune response). Indeed, similar to 50% of such genes commence with 2A. It appears, therefore, that this form of recoding plays a role in controlling protein biogenesis both in pathogens and in the innate immune system.