Genome-wide identification of Aedes albopictus long noncoding RNAs and their association with dengue and Zika virus infection.
Genome-wide identification of Aedes albopictus long noncoding RNAs and their association with dengue and Zika virus infection.
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DOI：
10.1371/journal.pntd.0008351
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发表时间：
2021-01
影响因子：
3.8
通讯作者：
Azzam G
中科院分区：
文献类型：
--
作者：
Azlan A;Obeidat SM;Theva Das K;Yunus MA;Azzam G
白纹伊蚊Aedes albopictus（Ae.白纹伊蚊（albopictus）是传播虫媒病毒如登革热（DENV）、寨卡病毒（ZIKV）和基孔肯雅病毒（CHIKV）的重要载体。已知长链非编码RNA（lncRNA）调节多种生物学过程。知识在Ae。白纹伊蚊lncRNA及其在病毒-宿主相互作用中的功能作用仍然有限。在这里，我们确定并表征了虫媒病毒载体Ae基因组中的lncRNA。白纹伊蚊，并评估它们在DENV和ZIKV感染中的潜在参与。我们使用了148个公开数据集，共鉴定了10，867个新的lncRNA转录本，其中5，809个为基因间转录本，4，139个为内含子转录本，919个为反义转录本。的Ae。白纹伊蚊lncRNA与其他物种lncRNA具有许多共同的特征，如长度短、GC含量低、序列保守性低。Ae.的RNA测序。用DENV和ZIKV感染的白纹伊蚊细胞显示lncRNA的表达在病毒感染后改变。靶标预测分析表明，Ae.白纹伊蚊lncRNA可以调节参与免疫和其他代谢和细胞过程的基因的表达。为了验证lncRNA在病毒感染中的作用，我们使用CRISPR-Cas9在lncRNA基因座中产生突变，并且发现两个lncRNA基因座突变，即XLOC_029733（新型lncRNA转录物id：lncRNA_27639.2）和LOC 115270134（已知lncRNA转录物id：XR_003899061.1）导致DENV和ZIKV复制的增强。本研究结果为进一步研究lncRNA及其与Ae病毒感染的关系奠定了基础。白纹伊蚊AE.白纹伊蚊是登革热和寨卡病毒等虫媒病毒的重要载体。在基因表达和分子水平上研究病毒与宿主的相互作用对设计抑制病毒在伊蚊体内复制的方法至关重要。以往的研究表明，除了蛋白质编码基因外，非编码RNA如lncRNA也参与了病毒与宿主的相互作用。在这项研究中，我们报告了一个全面的目录，新的lncRNA转录在基因组中的Ae。白纹伊蚊我们还表明，在感染登革热和寨卡病毒后，lncRNA的表达发生了变化。此外，某些lncRNA的消耗导致登革热和寨卡病毒的复制增加;因此，表明lncRNA在病毒感染中的潜在关联。本研究结果为蚊虫与病毒相互作用的研究提供了新的途径，尤其是在非编码基因方面。
The Asian tiger mosquito, Aedes albopictus (Ae. albopictus), is an important vector that transmits arboviruses such as dengue (DENV), Zika (ZIKV) and Chikungunya virus (CHIKV). Long noncoding RNAs (lncRNAs) are known to regulate various biological processes. Knowledge on Ae. albopictus lncRNAs and their functional role in virus-host interactions are still limited. Here, we identified and characterized the lncRNAs in the genome of an arbovirus vector, Ae. albopictus, and evaluated their potential involvement in DENV and ZIKV infection. We used 148 public datasets, and identified a total of 10, 867 novel lncRNA transcripts, of which 5,809, 4,139, and 919 were intergenic, intronic and antisense respectively. The Ae. albopictus lncRNAs shared many characteristics with other species such as short length, low GC content, and low sequence conservation. RNA-sequencing of Ae. albopictus cells infected with DENV and ZIKV showed that the expression of lncRNAs was altered upon virus infection. Target prediction analysis revealed that Ae. albopictus lncRNAs may regulate the expression of genes involved in immunity and other metabolic and cellular processes. To verify the role of lncRNAs in virus infection, we generated mutations in lncRNA loci using CRISPR-Cas9, and discovered that two lncRNA loci mutations, namely XLOC_029733 (novel lncRNA transcript id: lncRNA_27639.2) and LOC115270134 (known lncRNA transcript id: XR_003899061.1) resulted in enhancement of DENV and ZIKV replication. The results presented here provide an important foundation for future studies of lncRNAs and their relationship with virus infection in Ae. albopictus. Ae. albopictus is an important vector of arboviruses such as dengue and Zika viruses. Studies on virus-host interaction at gene expression and molecular level are crucial especially in devising methods to inhibit virus replication in Aedes mosquitoes. Previous reports have shown that, besides protein-coding genes, noncoding RNAs such as lncRNAs are also involved in virus-host interaction. In this study, we report a comprehensive catalog of novel lncRNA transcripts in the genome of Ae. albopictus. We also show that the expression of lncRNAs was altered upon infection with dengue and Zika. Additionally, depletion of certain lncRNAs resulted in increased replication of dengue and Zika; hence, suggesting potential association of lncRNAs in virus infection. Results of this study provide a new avenue to the investigation of mosquito-virus interactions, especially in the aspect of noncoding genes.
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