來自洛克菲勒大學(xué)植物分子生物學(xué)實驗室等處的研究人員發(fā)現(xiàn)了一種植物中用以逃避RNA沉默(RNA silencing)的新病毒策略,這一研究成果公布在新一期的《Genes & Development》雜志上,。
RNA沉默可以說就是在基因組水平的免疫現(xiàn)象,,不僅在動物體內(nèi)存在,而且在植物體內(nèi)也存在,,是一種原始的基因組對抗來自外來基因表達(dá)的保護(hù)機制,。對于植物而言,轉(zhuǎn)錄后基因沉默和病毒誘導(dǎo)的基因沉默是針對頻繁出現(xiàn)的病毒感染的保護(hù)機制,,這種防御系統(tǒng)的優(yōu)勢是其防御信號可以擴散,,如果接種一片樹葉的一個區(qū)域,能將免疫力給予周圍的細(xì)胞,。
雖然植物有這種防御手段,,但是仍然有一些病毒能抑制RNA沉默作用,這在以前的研究中就已經(jīng)被發(fā)現(xiàn)了,,然而在這篇研究報告中,,首次發(fā)現(xiàn)了一個沉默途徑中清晰綁定的受動蛋白(effector protein):研究人員在擬南芥和體外實驗中都證明黃瓜花葉病毒(Cucumber mosaic virus,CMV)(世界上分布最廣的植物病毒之一)蛋白2b可以結(jié)合并抑制Argonaute蛋白1,從而繞過植物的抗病毒應(yīng)答系統(tǒng),。
RNAi的機制目前研究認(rèn)為是細(xì)胞內(nèi)雙鏈RNA在Dicer酶的作用下,,可形成-22 bp大小的小干擾RNA(small interfering RNA,siRNA),,siRNAs可進(jìn)一步摻入多部分核酸酶(multicomponent nuclease)等形成的RNA沉默復(fù)合體(RNA-induced silencing complex,,RISC)并使其激活,從而精確降解與siRNAs序列相同的mRNA,,完全抑制了該基因在細(xì)胞內(nèi)的翻譯和表達(dá),。
在這個過程中,RNAi沉默復(fù)合物RISC有一個重要成份,,即稱為Argonaute的蛋白家族(或EIF2C蛋白),研究人員結(jié)合生物化學(xué)與遺傳學(xué)的方法發(fā)現(xiàn)CMV 2b可以通過與Argonaute 1作用,抑制內(nèi)源性的microRNA過程和病毒誘導(dǎo)的基因沉默過程,,但是具體的機制尚不清楚,。
科學(xué)家們一直以來都不清楚到底抗病毒的Slicer是什么,這一研究就證明最起碼Argonaute 1蛋白可以扮演Slicer的角色,,當(dāng)然這并不是說Argonaute 1就是唯一的抗病毒Slicer,,Argonaute家族的十幾種蛋白都有可能是。
英文原文:
The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster
Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens. Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.