nature

当前位置: Nature » 分子生物学 » 正文

中外科学家发现控制凶险型疟疾关键分子

摘要 : 近日,同济大学医学院附属东方医院转化医学研究中心、同济大学医学院传染病与疫苗研究所张青锋博士等与法国巴斯德研究所Artur Scherf教授合作,首次发现能控制凶险型疟疾的关键调控因子——“PfRNase II”。这将为凶险型疟疾的防治提供新的思路和治疗靶点,相关研究成果已发表于《自然》杂志。

近日,同济大学医学院附属东方医院转化医学研究中心、同济大学医学院传染病与疫苗研究所张青锋博士等与法国巴斯德研究所Artur Scherf教授合作,首次发现能控制凶险型疟疾的关键调控因子——“PfRNase II”。这将为凶险型疟疾的防治提供新的思路和治疗靶点,相关研究成果已发表于《自然》杂志。

中外科学家发现控制凶险型疟疾关键分子

据介绍,大量研究证实,恶性疟原虫变异基因家族(var)是恶性疟疾的关键致病基因,其中A亚类变异基因(A-var)是导致凶险型疟疾的“罪魁祸首”。

张青锋等利用现代生物技术,以A-var基因转录后调控作为切入点,对其表达调控机制进行了深入研究。通过基因组生物信息学分析,张青锋等在恶性疟原虫外切体复合物类似蛋白中发现了一个“多余”的成员。通过转基因和RNA测序技术,研究人员发现其调控对象正是A-var基因。

同时,研究人员利用疟疾病人血液中分离的疟原虫,对PfRNase II与A-var基因转录水平的相关性进行了初步分析后发现,“PfRNase II”与凶险型疟疾发病高度相关,它有望成为防治凶险型疟疾的新的重要靶分子。

张青锋表示:“这一研究发现有望为新型抗疟药物的研制、疟疾疫苗的研制,提供一个非常关键的靶点,从而在临床上有助于降低疟疾的发生率和死亡率。这也为疟疾基础研究向临床转化研究打下了一个非常好的基础。”

原文摘要:

Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

Qingfeng Zhang, T. Nicolai Siegel, Rafael M. Martins, Fei Wang, Jun Cao, Qi Gao, Xiu Cheng, Lubin Jiang, Chung-Chau Hon, Christine Scheidig-Benatar, Hiroshi Sakamoto,Louise Turner, Anja T. R. Jensen, Aurelie Claes, Julien Guizetti, Nicholas A. Malmquist &Artur Scherf

Antigenic variation of the Plasmodium falciparum multicopy var gene family enables parasite evasion of immune destruction by host antibodies. expression of a particular var subgroup, termed upsA, is linked to the obstruction of blood vessels in the brain and to the pathogenesis of human cerebral malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of PfRNase IIand upsA-type var genes in parasites from severe malaria patients, implying a crucial role of PfRNase II in severe malaria. Our results uncover a previously unknown type of post-transcriptional gene silencing mechanism in malaria parasites with repercussions for other organisms. Additionally, the identification of RNase II as a parasite protein controlling the expression of virulence genes involved in pathogenesis in patients with severe malaria may provide new strategies for reducing malaria mortality.

来源: 中国科学报 浏览次数:42

热门文章TOP

RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.