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| 購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物 www.mobfastly.com |
近日，同濟大學醫學院附屬東方醫院轉化醫學研究中心、同濟大學醫學院傳染病與疫苗研究所張青鋒博士等與法國巴斯德研究所Artur Scherf教授合作，首次發現能控制兇險型瘧疾的關鍵調控因子——“PfRNase II”。這將為兇險型瘧疾的防治提供新的思路和治療靶點，相關研究成果已發表于《自然》雜志。  據介紹，大量研究證實，惡性瘧原蟲變異基因家族(var)是惡性瘧疾的關鍵致病基因，其中A亞類變異基因(A-var)是導致兇險型瘧疾的“罪魁禍首”。 張青鋒等利用現代生物技術，以A-var基因轉錄后調控作為切入點，對其表達調控機制進行了深入研究。通過基因組生物信息學分析，張青鋒等在惡性瘧原蟲外切體復合物類似蛋白中發現了一個“多余”的成員。通過轉基因和RNA測序技術，研究人員發現其調控對象正是A-var基因。 同時，研究人員利用瘧疾病人血液中分離的瘧原蟲，對PfRNase II與A-var基因轉錄水平的相關性進行了初步分析后發現，“PfRNase II”與兇險型瘧疾發病高度相關，它有望成為防治兇險型瘧疾的新的重要靶分子。 張青鋒表示：“這一研究發現有望為新型抗瘧藥物的研制、瘧疾疫苗的研制，提供一個非常關鍵的靶點，從而在臨床上有助于降低瘧疾的發生率和死亡率。這也為瘧疾基礎研究向臨床轉化研究打下了一個非常好的基礎。” 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. |
購買進口儀器、試劑和耗材——就在始于2001年的畢特博生物
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