Zhang Lingrui, Chen Hui, Brandizzi Federica, Verchot Jeanmarie, Wang Aiming
Southern Crop Protection and Food Research, Agriculture and Agri-Food Canada, London, Ontario, Canada.
Department of Energy Plant Research Laboratory and Department of Plant Biology, Michigan State University, East Lansing, Michigan, USA.
PLoS Genet. 2015 Apr 15;11(4):e1005164. doi: 10.1371/journal.pgen.1005164. eCollection 2015 Apr.
The unfolded protein response (UPR) signaling network encompasses two pathways in plants, one mediated by inositol-requiring protein-1 (IRE1)-bZIP60 mRNA and the other by site-1/site-2 proteases (S1P/S2P)-bZIP17/bZIP28. As the major sensor of UPR in eukaryotes, IRE1, in response to endoplasmic reticulum (ER) stress, catalyzes the unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans. Recent studies suggest that IRE1p and HAC1 mRNA, the only UPR pathway found in yeast, evolves as a cognate system responsible for the robust UPR induction. However, the functional connectivity of IRE1 and its splicing target in multicellular eukaryotes as well as the degree of conservation of IRE1 downstream signaling effectors across eukaryotes remains to be established. Here, we report that IRE1 and its substrate bZIP60 function as a strictly cognate enzyme-substrate pair to control viral pathogenesis in plants. Moreover, we show that the S1P/S2P-bZIP17/bZIP28 pathway, the other known branch of UPR in plants, does not play a detectable role in virus infection, demonstrating the distinct function of the IRE1-bZIP60 pathway in plants. Furthermore, we provide evidence that bZIP60 and HAC1, products of the enzyme-substrate duet, rather than IRE1, are functionally replaceable to cope with ER stress in yeast. Taken together, we conclude that the downstream signaling of the IRE1-mediated splicing is evolutionarily conserved in yeast and plants, and that the IRE1-bZIP60 UPR pathway not only confers overlapping functions with the other UPR branch in fundamental biology but also may exert a unique role in certain biological processes such as virus-plant interactions.
未折叠蛋白反应（UPR）信号网络在植物中包含两条途径，一条由肌醇需求蛋白-1（IRE1）-bZIP60信使核糖核酸介导，另一条由位点-1/位点-2蛋白酶（S1P/S2P）-bZIP17/bZIP28介导。作为真核生物中UPR的主要传感器，IRE1响应内质网（ER）应激，催化酵母中的HAC1、植物中的bZIP60和后生动物中的XBP1的非常规剪接。最近的研究表明，酵母中发现的唯一UPR途径IRE1p和HAC1信使核糖核酸，进化为负责强大UPR诱导的同源系统。然而，IRE1及其剪接靶点在多细胞真核生物中的功能连接性以及IRE1下游信号效应器在真核生物中的保守程度仍有待确定。在这里，我们报告IRE1及其底物bZIP60作为严格的同源酶-底物对发挥作用，以控制植物中的病毒发病机制。此外，我们表明，植物中UPR的另一个已知分支S1P/S2P-bZIP17/bZIP28途径在病毒感染中未发挥可检测到的作用，这证明了IRE1-bZIP60途径在植物中的独特功能。此外，我们提供证据表明，酶-底物对偶的产物bZIP60和HAC1，而不是IRE1，在功能上可替代以应对酵母中的内质网应激。综上所述，我们得出结论，IRE1介导的剪接的下游信号在酵母和植物中是进化保守的，并且IRE1-bZIP60 UPR途径不仅在基础生物学中与其他UPR分支具有重叠功能，而且可能在某些生物学过程如病毒-植物相互作用中发挥独特作用。
