PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA.
PRMT1 methylates the single Argonaute of Toxoplasma gondii and is important for the recruitment of Tudor nuclease for target RNA cleavage by antisense guide RNA.
复制标题
DOI：
10.1111/j.1462-5822.2012.01763.x
复制
发表时间：
2012-06
影响因子：
3.4
通讯作者：
Barik S
中科院分区：
文献类型：
--
作者：
Musiyenko A;Majumdar T;Andrews J;Adams B;Barik S
Argonaute （Ago）在后生动物的RNA干扰中起核心作用，但其在低等生物中的地位仍不明确。我们报道了单细胞原生动物弓形虫（Tg）的Ago复合物，弓形虫是哺乳动物宿主的一种强制性病原体。TgAgo的piwi样结构域缺乏典型的DDE/H催化三联体，这解释了它的弱靶RNA切割活性。然而，TgAgo与更强的RNA切片器、Tudor葡萄球菌核酸酶（TSN）和蛋白质精氨酸甲基转移酶PRMT1相关。突变分析表明，TgAgo的n端RGG-repeat结构域被PRMT1甲基化，与TSN的募集有关。TgAgo的切片活性依赖于Mg2+，并且需要引导RNA和靶标之间的完美互补。相反，TSN活性依赖于Ca2+，需要不完全配对的引导RNA。以前敲除的寄生虫表现出基本正常的生长，但相比之下，PRMT1敲除的寄生虫生长异常。化学抑制精氨酸甲基化也有抗寄生作用。这些结果表明，寄生PRMT1具有多种作用，其缺失会影响寄生RNA沉默复合体招募更有效的第二切片机，其确切机制仍有待确定。
Argonaute (Ago) plays a central role in RNA interference in metazoans, but its status in lower organisms remains ill-defined. We report on the Ago complex of the unicellular protozoan, Toxoplasma gondii (Tg), an obligatory pathogen of mammalian hosts. The PIWI-like domain of TgAgo lacked the canonical DDE/H catalytic triad, explaining its weak target RNA cleavage activity. However, TgAgo associated with a stronger RNA slicer, a Tudor staphylococcal nuclease (TSN), and with a protein Arg methyl transferase, PRMT1. Mutational analysis suggested that the N-terminal RGG-repeat domain of TgAgo was methylated by PRMT1, correlating with the recruitment of TSN. The slicer activity of TgAgo was Mg2+-dependent and required perfect complementarity between the guide RNA and the target. In contrast, the TSN activity was Ca2+-dependent and required an imperfectly paired guide RNA. Ago knockout parasites showed essentially normal growth, but in contrast, the PRMT1 knockouts grew abnormally. Chemical inhibition of Arg-methylation also had an anti-parasitic effect. These results suggest that the parasitic PRMT1 plays multiple roles, and its loss affects the recruitment of a more potent second slicer to the parasitic RNA silencing complex, the exact mechanism of which remains to be determined.
登录
查看更多内容
影响因子：
4
作者：
Al Riyahi, Ahmad;Al-Anouti, Fatme;Ananvoranich, Sirinart
通讯作者：
Ananvoranich, Sirinart
影响因子：
10.5
作者：
Caudy, AA;Myers, M;Hammond, SM
通讯作者：
Hammond, SM
影响因子：
1.5
作者：
Janzen, Christian J.;van Deursen, Frederick;Shi, Huafang;Cross, George A. M.;Matthews, Keith R.;Ullu, Elisabetta
通讯作者：
Ullu, Elisabetta
影响因子：
--
作者：
Fox, Barbara A.;Ristuccia, Jessica G.;Bzik, David J.
通讯作者：
Bzik, David J.
影响因子：
--
作者：
Huynh, My-Hang;Carruthers, Vern B.
通讯作者：
Carruthers, Vern B.