Yin Shigang, Fan Yanting, He Xiaohui, Wei Guiying, Wen Yuhao, Zhao Yuemeng, Shi Mingli, Wei Jieqiong, Chen Huiling, Han Jiping, Jiang Lubin, Zhang Qingfeng
Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine , Shanghai, China.
Unit of Human Parasite Molecular and Cell Biology, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Shanghai, China.
RNA Biol. 2020 Jun;17(6):828-842. doi: 10.1080/15476286.2020.1732032. Epub 2020 Feb 27.
The tight gene expression regulation controls the development and pathogenesis of human malaria parasite throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of , suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.
严格的基因表达调控在人类疟原虫复杂的生命周期中控制着其发育和发病机制。最近的研究揭示了疟原虫基因组中普遍存在的新生转录本,这表明存在一个参与动态基因表达的隐藏转录组。然而,新生非编码RNA(ns-ncRNAs)的图谱及其相关生物学功能仍未得到充分探索。在此,我们通过去除rRNA和链特异性RNA测序,对疟原虫红细胞内发育周期(IDC)48小时内的新生RNA转录动态进行了分析。我们鉴定出了总共2252个ns-ncRNAs的全基因组来源,它们大多源自注释基因的基因间区域和非翻译区。通过将新生RNA丰度与ATAC-seq和ChIP-seq分析相结合,我们发现了ns-ncRNA基因座周围的常染色质微环境,并揭示了ns-ncRNAs与相应mRNA丰度之间的正相关关系。最后,通过基因敲降策略,我们表明RNA外泌体催化亚基PfDis3和PfMtr4辅助因子的协同作用在ns-ncRNAs降解中起主要作用。总的来说,这项研究有助于理解短命新生ncRNAs在疟原虫基因表达调控中的潜在作用。