Structural diversity and phylogenetic distribution of valyl tRNA-like structures in viruses.
Structural diversity and phylogenetic distribution of valyl tRNA-like structures in viruses.
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DOI：
10.1261/rna.076968.120
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Kieft JS
中科院分区：
文献类型：
--
作者：
Sherlock ME;Hartwick EW;MacFadden A;Kieft JS
病毒通常使用特异性折叠的RNA元件，其与宿主和病毒蛋白质相互作用以执行对不同病毒过程重要的功能。例如在某些正义ssRNA病毒基因组的3′末端发现，它们部分模拟tRNA，包括被宿主细胞酶氨酰化。缬氨酸接受tRNA样结构（TLSVal）是一个例子，它与典型的tRNA有一些明显的同源性，但有几个重要的结构差异。虽然已经鉴定了许多TLSVal的例子，但我们对其结构多样性和系统发育分布缺乏充分的了解。为了解决这个问题，我们对这些RNA进行了深入的生物信息学和生物化学研究，并以最近TLSVal的高分辨率结构为指导。我们在感染植物的病毒和不相关的昆虫特异性病毒中编目了许多新的例子。使用生物化学和结构方法，我们验证了代表性TLSVal底物的二级结构，并测试了它们被缬氨酰化的能力，证实了以前在该类中观察到的结构异质性。在少数情况下，大的茎环结构插入位于TLS远端已知宿主细胞因子结合位点的区域中的可变区内。此外，我们发现了一种病毒，其TLS将其反密码子从缬氨酸转换，导致缬氨酰化活性丧失;这一影响尚不清楚。这些结果完善了我们对tRNA模拟的结构和功能机制细节以及如何在病毒感染中使用的理解。
Viruses commonly use specifically folded RNA elements that interact with both host and viral proteins to perform functions important for diverse viral processes. Examples are found at the 3′ termini of certain positive-sense ssRNA virus genomes where they partially mimic tRNAs, including being aminoacylated by host cell enzymes. Valine-accepting tRNA-like structures (TLSVal) are an example that share some clear homology with canonical tRNAs but have several important structural differences. Although many examples of TLSVal have been identified, we lacked a full understanding of their structural diversity and phylogenetic distribution. To address this, we undertook an in-depth bioinformatic and biochemical investigation of these RNAs, guided by recent high-resolution structures of a TLSVal. We cataloged many new examples in plant-infecting viruses but also in unrelated insect-specific viruses. Using biochemical and structural approaches, we verified the secondary structure of representative TLSVal substrates and tested their ability to be valylated, confirming previous observations of structural heterogeneity within this class. In a few cases, large stem–loop structures are inserted within variable regions located in an area of the TLS distal to known host cell factor binding sites. In addition, we identified one virus whose TLS has switched its anticodon away from valine, causing a loss of valylation activity; the implications of this remain unclear. These results refine our understanding of the structural and functional mechanistic details of tRNA mimicry and how this may be used in viral infection.
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