SARS-CoV-2 competes with host mRNAs for efficient translation by maintaining the mutations favorable for translation initiation.
SARS-CoV-2 competes with host mRNAs for efficient translation by maintaining the mutations favorable for translation initiation.
复制标题
DOI：
10.1007/s13353-021-00665-w
复制
发表时间：
2022-03
影响因子：
2.4
通讯作者：
Yin B
中科院分区：
文献类型：
--
作者：
Zhang Y;Jin X;Wang H;Miao Y;Yang X;Jiang W;Yin B
在SARS-CoV-2增殖过程中，病毒RNA的翻译通常是限速步骤。了解这一步骤的分子细节有助于揭示SARS-CoV-2的起源和进化，甚至有助于控制大流行。到目前为止，还不清楚SARS-CoV-2如何与宿主mRNA竞争核糖体结合和有效翻译。我们检索了所有人类基因和SARS-CoV-2基因的编码序列。我们系统地分析了每个CDS的GC含量和折叠能。考虑到SARS-CoV-2和人类基因组中存在一些固定或多态性突变，所有算法和分析均适用于突变前和突变后版本。在SARS-CoV-2中，CDS的5-prime末端比3-prime部分具有更低的GC含量和更少的RNA结构，这有利于核糖体结合和有效的翻译起始。在全球范围内，SARS-CoV-2中的固定和多态性突变在CDS的5-prime末端产生了更低的GC含量。与此相反，在人类基因组中的固定突变和多态性突变没有观察到类似的模式。与人RNA相比，SARS-CoV-2 RNA的5 ′端结构较少，因此更有利于快速翻译起始。SARS-CoV-2中的固定突变和多态突变进一步放大了这一优势。这可能是SARS-CoV-2适应人类宿主的一种策略。
During SARS-CoV-2 proliferation, the translation of viral RNAs is usually the rate-limiting step. Understanding the molecular details of this step is beneficial for uncovering the origin and evolution of SARS-CoV-2 and even for controlling the pandemic. To date, it is unclear how SARS-CoV-2 competes with host mRNAs for ribosome binding and efficient translation. We retrieved the coding sequences of all human genes and SARS-CoV-2 genes. We systematically profiled the GC content and folding energy of each CDS. Considering that some fixed or polymorphic mutations exist in SARS-CoV-2 and human genomes, all algorithms and analyses were applied to both pre-mutate and post-mutate versions. In SARS-CoV-2 but not human, the 5-prime end of CDS had lower GC content and less RNA structure than the 3-prime part, which was favorable for ribosome binding and efficient translation initiation. Globally, the fixed and polymorphic mutations in SARS-CoV-2 had created an even lower GC content at the 5-prime end of CDS. In contrast, no similar patterns were observed for the fixed and polymorphic mutations in human genome. Compared with human RNAs, the SARS-CoV-2 RNAs have less RNA structure in the 5-prime end and thus are more favorable of fast translation initiation. The fixed and polymorphic mutations in SARS-CoV-2 are further amplifying this advantage. This might serve as a strategy for SARS-CoV-2 to adapt to the human host.
登录
查看更多内容
影响因子：
5.5
作者：
Alonso, Andres Mariano;Diambra, Luis
通讯作者：
Diambra, Luis
影响因子：
2.4
作者：
Jiang, Yankai;Cao, Xinyue;Wang, Haibin
通讯作者：
Wang, Haibin
影响因子：
5.4
作者：
Carmi, Gon;Gorohovski, Alessandro;Frenkel-Morgenstern, Milana
通讯作者：
Frenkel-Morgenstern, Milana
影响因子：
64.8
作者：
HALL, MN;GABAY, J;SCHWARTZ, M
通讯作者：
SCHWARTZ, M
影响因子：
9.8
作者：
MacLean OA;Lytras S;Weaver S;Singer JB;Boni MF;Lemey P;Kosakovsky Pond SL;Robertson DL
通讯作者：
Robertson DL