The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum
The cryptic unstable transcripts are associated with developmentally regulated gene expression in blood-stage Plasmodium falciparum
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神秘的不稳定转录本与血液阶段恶性疟原虫中发育调节的基因表达有关
DOI：
10.1080/15476286.2020.1732032
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发表时间：
2020-03-01
期刊：
影响因子：
4.1
通讯作者：
Zhang, Qingfeng
中科院分区：
文献类型：
--
作者：
Yin, Shigang;Fan, Yanting;Zhang, Qingfeng
恶性疟原虫基因表达调控系统控制着恶性疟原虫的发育和致病过程。近年来的研究发现恶性疟原虫基因组中普遍存在新生转录本，提示恶性疟原虫基因组中存在一个参与基因动态表达的隐藏转录组。然而，新生非编码RNA（ns-ncRNA）的景观和相关的生物学功能仍然很少探索。在这里，我们描绘的转录动力学的新生RNA的rRNA耗尽和链RNA测序过程中的48小时红细胞内发育周期（IDC）。我们确定了总共2252个ns-ncRNA的全基因组来源，大部分来源于注释基因的基因间和非翻译区。通过将新生RNA丰度与ATAC-seq和ChIP-seq分析相结合，我们揭示了ns-ncRNA位点周围的常染色质微环境，并揭示了ns-ncRNA与相应mRNA丰度之间的正相关性。最后，通过基因敲低策略，我们发现RNA外泌体催化亚基PfDis 3和PfMtr 4辅因子的协同作用在ns-ncRNA的降解中起主要作用。总的来说，这项研究有助于了解短寿命的新生ncRNA在调节疟疾寄生虫基因表达中的潜在作用。
ABSTRACT The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, 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.