研究揭示SARS-CoV-2的編碼能力
作者：
小柯機器人發布時間：2020/9/12 22:32:38
以色列魏茨曼科學研究院Noam Stern-Ginossar團隊揭示SARS-CoV-2的編碼能力。這一研究成果於2020年9月9日在線發表在國際學術期刊《自然》上。
研究人員表示，嚴重急性呼吸系統綜合症冠狀病毒2（SARS-CoV-2）是導致2019冠狀病毒病（COVID-19）大流行的原因。為了解SARS-CoV-2的致病性和抗原潛力，並開發治療工具，必須描繪其表達蛋白的全部組成。目前，SARS-CoV-2編碼能力圖譜是基於計算預測，並依賴於與其他冠狀病毒的同源性。由於冠狀病毒的蛋白質陣列不同，尤其是輔助蛋白質的種類不同，因此以無偏倚和開放性的方式表徵SARS-CoV-2蛋白特定集合至關重要。
使用一套核糖體譜分析技術，研究人員展示了SARS-CoV-2編碼區的高解析度圖譜，這能夠準確地定量經典病毒開放閱讀框（ORF）的表達並鑑定23種未注釋的病毒ORF 。這些ORF包括可能起調節作用的上遊ORF（uORF）、位於現有ORF內的多個框內內部ORF（導致N末端被截短的產物）以及內部框外ORF（它們產生新的多肽） 。
研究人員進一步表明，病毒mRNA不能比宿主mRNA更有效地翻譯。相反，由於高水平的病毒轉錄本，病毒翻譯在宿主翻譯中佔主導地位。這項工作提供了豐富的資源，將構成未來功能研究的基礎。
附：英文原文
Title: The coding capacity of SARS-CoV-2
Author: Yaara Finkel, Orel Mizrahi, Aharon Nachshon, Shira Weingarten-Gabbay, David Morgenstern, Yfat Yahalom-Ronen, Hadas Tamir, Hagit Achdout, Dana Stein, Ofir Israeli, Adi Beth-Din, Sharon Melamed, Shay Weiss, Tomer Israely, Nir Paran, Michal Schwartz, Noam Stern-Ginossar
Issue&Volume: 2020-09-09
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing Coronavirus disease 19 (COVID-19) pandemic1. In order to understand SARS-CoV-2 pathogenicity and antigenic potential, and to develop therapeutic tools, it is essential to portray the full repertoire of its expressed proteins. The SARS-CoV-2 coding capacity map is currently based on computational predictions and relies on homology to other coronaviruses. Since coronaviruses differ in their protein array, especially in the variety of accessory proteins, it is crucial to characterize the specific collection of SARS-CoV-2 proteins in an unbiased and open-ended manner. Using a suite of ribosome profiling techniques2–4, we present a high-resolution map of the SARS-CoV-2 coding regions, allowing us to accurately quantify the expression of canonical viral open reading frames (ORFs) and to identify 23 unannotated viral ORFs. These ORFs include upstream ORFs (uORFs) that are likely playing a regulatory role, several in-frame internal ORFs lying within existing ORFs, resulting in N-terminally truncated products, as well as internal out-of-frame ORFs, which generate novel polypeptides. We further show that viral mRNAs are not translated more efficiently than host mRNAs; rather, virus translation dominates host translation due to high levels of viral transcripts. Our work provides a rich resource, which will form the basis of future functional studies.
DOI: 10.1038/s41586-020-2739-1
Source: https://www.nature.com/articles/s41586-020-2739-1