A map of the SARS-CoV-2 RNA structurome.

A map of the SARS-CoV-2 RNA structurome.
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SARS-CoV-2RNA结构图。

DOI:
10.1093/nargab/lqab043
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发表时间:
2021-06
影响因子:
4.6
通讯作者:
Moss WN
Moss WN
中科院分区:
其他
文献类型:
--
作者:
Andrews RJ;O'Leary CA;Tompkins VS;Peterson JM;Haniff HS;Williams C;Disney MD;Moss WN

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SARS-CoV-2已经在整个人类群体中爆发。为了促进对SARS-CoV-2生物学的深入了解和治疗靶向病毒的努力,有必要在其RNA基因组中嵌入可能的功能区域的路线图。在这份报告中,我们使用了生物信息学方法ScanFold来推断SARS-CoV-2基因组中具有最高可能性的局部RNA结构景观。我们概括了以前已知的RNA结构的元素,并提供了一个重要的移码信号的折叠模型。我们的研究结果发现,SARS-CoV-2极大地富集了异常稳定且可能进化有序的RNA结构,这为RNA结合小分子提供了大量潜在的药物靶点。通过重新分析公开的全基因组生化结构探测数据集,结果得到了增强,这些数据集与我们的模型基本一致。此外,更新了ScanFold,将实验数据作为分析中的约束条件,以便于比较ScanFold和其他RNA建模方法。最终,ScanFold能够在SARS-CoV-2中识别出8个高度结构化/保守的基序,这些基序与实验数据一致,而无需明确使用这些数据。所有结果均可通过公共数据库(RNAStructuromeDB:https://structurome.bb.iastate.edu/sars-cov-2)获得,模型比较可在https://structurome.bb.iastate.edu/sars-cov-2-global-model-comparisons上查看。
SARS-CoV-2 has exploded throughout the human population. To facilitate efforts to gain insights into SARS-CoV-2 biology and to target the virus therapeutically, it is essential to have a roadmap of likely functional regions embedded in its RNA genome. In this report, we used a bioinformatics approach, ScanFold, to deduce the local RNA structural landscape of the SARS-CoV-2 genome with the highest likelihood of being functional. We recapitulate previously-known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a large reservoir of potential drug targets for RNA-binding small molecules. Results are enhanced via the re-analyses of publicly-available genome-wide biochemical structure probing datasets that are broadly in agreement with our models. Additionally, ScanFold was updated to incorporate experimental data as constraints in the analysis to facilitate comparisons between ScanFold and other RNA modelling approaches. Ultimately, ScanFold was able to identify eight highly structured/conserved motifs in SARS-CoV-2 that agree with experimental data, without explicitly using these data. All results are made available via a public database (the RNAStructuromeDB: https://structurome.bb.iastate.edu/sars-cov-2) and model comparisons are readily viewable at https://structurome.bb.iastate.edu/sars-cov-2-global-model-comparisons.
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发表时间: 2010-02-05
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