抗病毒物質Degradation of the antiviral component ARGONAUTE1會經由自噬作用被降解掉 by the autophagy pathway

Derrien B,  et al.

PNAS.  2012 Sep 25,;109(39): 15942-6

Speaker演講者:  Szu-Han Kuo (郭思含)                                          Time時間: 2013/4/3, 14:00-15:00

Commentator講評老師:  Dr. Pin-Ling (凌斌老師)                                  Location地點: Room 601

Abstract摘要

     ARGONAUTE (AGO)蛋白質家族的成員參與後轉錄基因抑制作用 protein family takes part in posttranscriptional gene silencing (PTGS))，, 而此作用對於調控動、植物的發育是重要的。PTGS 這項RNA抑制的機制同時也參與在植物與無脊椎動物的抗病毒功能中which is important for the regulation of development in animal and plants。本實驗中使用的植物模式是阿拉伯芥. The mechanism of RNA silencing also involves in antiviral functions in plants and invertebrates. In Arabidopsis，此植物的, AGO1是RISC複合物中的一個重要因子，RISC與siRNA結合後會將整個複合體帶往其目標RNA (例如病毒RNA)，若complex與目標RNA是高度互補的結合模式，會使的目標RNA被降解掉；然而，若是互補性低的結合模式則會導致目標RNA轉譯受抑制但不會被降解掉。一旦遇上宿主的抵禦機制 is a key component of RNA-induced silencing complex (RISC), which binds to siRNAs and guides the complex to partially or fully silence complementary RNA such as viral RNA，部分病毒會製造VSRs，用以干擾宿主細胞抗病毒的RNA抑制作用。自噬作用是一種維持細胞恆定的機制，近期研究發現自噬體除了能非專一性的吞噬目標蛋白，也可以專一性吞入標定上poly. As a counter defense, viruses have developed viral suppressors of RNA silencing (VSRs) to disturb host PTGS defense response. Autophagy is a cellular homeostasis process that canto degrade the engulfed cargos such as ubiquitinatedproteins的目標蛋白，而後與lysosome融合而將之降解。 by fusion with lysosomes. Polerovirus, 是種隸屬Luteoviridae家族的植物病毒，病毒遺傳物質為正單股RNA且無外套膜包裹an (+)ssRNA non-enveloped plant virus that, belongs to Luteoviridae family。. 由此病毒所產生的VSRs-P0屬於一種F box protein，目前所知Polerovirus的P0蛋白會造成宿主的The virusal-encoded VSR protein P0, which is an F box protein, which targets AGO1ARGONAUTE for degradation被降解掉。根據先前研究指出，. According to the previous study, polerovirus P0蛋白會劫取宿主SCF E3 ubiquitin ligase protein can form a SCF-like E3 ubiquitin ligase並使宿主參與RNA抑制作用的相關蛋白被 with the host factors that involved in the specific ubiquitylation， 進而使之被降解 of the silencing-related protein then leads to degradation (1)。近期研究也發現P0蛋白會抑制siRNA/miRNA-RISC複合體的形成，最終導致AGO1蛋白被降解 . RA recently study reports that P0 protein inhibits the formation of siRNA/miRNA-RISC, and ultimately leadsing to AGO1 degradation (2)。. 在本篇研究中In this paper，,作者利用 the authors used the P0-inducible的 transgenic cell line阿拉伯芥改造株(利用β-estradiol處理此改造的系統可誘發P0蛋白的表現)，觀察在植物中AGO1被降解的機制, in which P0 expression can be induced by β-estradiol treatment, followed by to 。實驗結果顯示AGO1的降解過程中需要SCF-type E3 ligase將polyubiquitin標定在其上。investigation ofe the process of AGO1 degradation in Arabidopsis. 電顯觀察也發現P0的表現會造成包裹著AGO1蛋白的囊泡累積在細胞質The results show that the process of AGO1 degradation requires ubiquitylation by an SCF-type E3 ligase。而利用自噬作用的抑制劑處理或是過度表現TOR，都會導致由P0調控的AGO1降解路徑被抑制。. Electron microscopy studyies observe revealed that P0 expression leads to an the accumulation of vacuolar inclusion containing AGO1.除了在病毒因子P0的存在下AGO1會經由自噬路徑被降解掉之外，同時也發現即使沒有P0的存在，AGO1一樣也會經由自噬路徑被降解掉 Furthermore, P0-mediated degradation of AGO1 is blocked by autophagy inhibitors or the overexpression of rapamycin (TOR) pathway. 。In addition to the viral context, under the nonviral context that the absence ofwithout[1] P0 protein, the AGO1 is also degraded by the autophagy pathway.

In summary, the authors reveal that the viral suppressor of RNA silencingVSRs protein P0 triggers AGO1 degradation by the autophagy pathway in Arabidopsis.

References參考資料

1.         Baumberger, N., C. H. Tsai, M. Lie, E. Havecker, and D. C. Baulcombe. 2007. The Polerovirus silencing suppressor P0 targets ARGONAUTE proteins for degradation. Current biology : CB 17:1609-1614.

2.         Csorba, T., R. Lozsa, G. Hutvagner, and J. Burgyan. 2010. Polerovirus protein P0 prevents the assembly of small RNA-containing RISC complexes and leads to degradation of ARGONAUTE1. The Plant journal : for cell and molecular biology 62:463-472.