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Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites.
mBio ( IF 6.4 ) Pub Date : 2020-06-02 , DOI: 10.1128/mbio.01110-20
Yanting Fan 1 , Shijun Shen 2 , Guiying Wei 1 , Jianxia Tang 3 , Yuemeng Zhao 1 , Fei Wang 1 , Xiaohui He 1 , Gangqiang Guo 2 , Xiaomin Shang 1 , Xinyu Yu 3 , Zhenlin Ma 4 , Xiaoqin He 3 , Meng Liu 2 , Qianshu Zhu 2 , Zhen Le 1 , Gang Wei 4 , Jun Cao 3, 5, 6 , Cizhong Jiang 7, 8 , Qingfeng Zhang 9
Affiliation  

The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite’s development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Plasmodium falciparum Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase, controls the silencing of heterochromatic genes. PfRrp6 knockdown disrupted the singular expression of the GC-rich ncRNA RUF6 family, a known critical regulator of virulence gene expression, through the stabilization of the nascent transcripts. Mechanistic investigation showed that the accumulation of the multiple RUF6 ncRNAs triggered local chromatin remodeling in situ, which activated their adjacent var genes. Strikingly, chromatin isolation by RNA purification analysis (ChIRP-seq) revealed that a remarkable RUF6 ncRNA had interacted with distal heterochromatin regions directly and stimulated a global derepression effect on heterochromatic genes, including all variant gene families and the sexual commitment-associated regulator ap2-g gene. Collectively, Rrp6 appears to conduct the epigenetic surveillance of heterochromatic gene expression through controlling RUF6 levels, thereby securing antigenic variation and sexual commitment of malaria parasites during the infection of the host.

中文翻译:

Rrp6通过ncRNA RUF6衰变调节疟原虫中的异色基因沉默。

异染色质环境在沉默与疟原虫的发生,宿主中的存活以及向蚊媒的传播相关的基因中起着核心作用。然而,尚不清楚调节动态染色质结构的潜在机制。在这里,我们发现恶性疟原虫Rrp6(真核RNA外泌体相关RNase的直系同源基因)控制异色基因的沉默。PfRrp6敲低通过稳定初生转录本,破坏了富含GC的ncRNA RUF6家族的奇异表达,这是一种已知的致病基因表达的关键调节因子。机理研究表明,多个RUF6 ncRNA的积累触发了原位染色质的原位重塑,从而激活了其相邻的var基因。引人注目的是,通过RNA纯化分析(ChIRP-seq)进行的染色质分离显示,杰出的RUF6 ncRNA与远端异染色质区域直接相互作用,并刺激了对异色基因的全局抑制作用,包括所有变异基因家族和与性相关的调节子ap2- g基因。总体而言,Rrp6似乎通过控制RUF6的水平来进行异色基因表达的表观遗传学监测,从而在宿主感染期间确保了疟原虫的抗原变异和有性承诺。
更新日期:2020-06-30
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