Parent tRNA Modification Status Determines the Induction of Functional tRNA-Derived RNA by Respiratory Syncytial Virus Infection.

Parent tRNA Modification Status Determines the Induction of Functional tRNA-Derived RNA by Respiratory Syncytial Virus Infection.
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DOI:
10.3390/v15010057
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发表时间:
2022-12-24
期刊:
Viruses
影响因子:
--
通讯作者:
Bao X
Bao X
中科院分区:
其他
文献类型:
--
作者:
Choi EJ;Wu W;Zhang K;Yuan X;Deng J;Ismail D;Buck DL;Thomason KS;Garofalo RP;Zhang S;Bao X

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转运RNA衍生的RNA片段(tRFs)是最近发现的一个小非编码RNA(sncRNAs)家族。我们先前报道过,呼吸道合胞病毒(RSV)感染会在上皮细胞中诱导功能性tRFs,这些tRFs来源于有限的亲本转运RNA子集。在RSV患者的鼻咽冲洗样本中也观察到这种诱导现象,并且与RSV基因组拷贝数相关,这表明tRFs在RSV感染中具有临床意义。这项工作还以一种最易诱导的tRF作为模型,研究RSV是否会改变亲本转运RNA的修饰从而诱导tRFs。我们发现RSV感染改变了谷氨酸转运RNA(其密码子为CTC,即tRNA - GluCTC)中第57位腺嘌呤的甲基化修饰,并且这种改变对其切割至关重要。先前报道的一种转运RNA去甲基化酶——AlkB同源物1似乎从tRNA - GluCTC中去除甲基腺嘌呤,促使随后从tRNA - GluCTC的5′端产生tRFs,而tRNA - GluCTC是RSV复制的调节因子。这项研究首次证明了在RSV感染后,转运RNA的转录后修饰在tRF生物发生中的重要性,为抗病毒策略的开发提供了关键见解。
tRNA-derived RNA fragments (tRFs) are a recently discovered family of small noncoding RNAs (sncRNAs). We previously reported that respiratory syncytial virus (RSV) infection induces functional tRFs, which are derived from a limited subset of parent tRNAs, in airway epithelial cells. Such induction is also observed in nasopharyngeal wash samples from RSV patients and correlates to RSV genome copies, suggesting a clinical significance of tRFs in RSV infection. This work also investigates whether the modification of parent tRNAs is changed by RSV to induce tRFs, using one of the most inducible tRFs as a model. We discovered that RSV infection changed the methylation modification of adenine at position 57 in tRNA glutamic acid, with a codon of CTC (tRNA-GluCTC), and the change is essential for its cleavage. AlkB homolog 1, a previously reported tRNA demethylase, appears to remove methyladenine from tRNA-GluCTC, prompting the subsequent production of tRFs from the 5′-end of tRNA-GluCTC, a regulator of RSV replication. This study demonstrates for the first time the importance of post-transcriptional modification of tRNAs in tRF biogenesis following RSV infection, providing critical insights for antiviral strategy development.
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