9月14日，Nucleic Acids Research在線發(fā)表華中農(nóng)大作物遺傳改良國家重點(diǎn)實(shí)驗(yàn)室周道繡課題組題為“Rice NAD+-dependent histone deacetylase OsSRT1 represses glycolysis and regulates the moonlighting function of GAPDH as a transcriptional activator of glycolytic genes”最新研究成果。該項(xiàng)研究揭示了水稻組蛋白去乙?；窸sSRT1通過介導(dǎo)組蛋白和糖酵解中的關(guān)鍵酶3-磷酸甘油醛脫氫酶（GAPDH）的去乙?；苯右种扑咎墙徒獯x途徑，從而調(diào)控水稻能量代謝的表觀調(diào)控機(jī)制，在作物中首次揭示了表觀調(diào)控與能量代謝的關(guān)系。

Fig.Schematic representation of OsSRT1 actions in repression of glycolysis in rice.

組蛋白去乙?；且环N重要的染色質(zhì)表觀修飾形式。一般情況下,該修飾可以增強(qiáng)DNA與組蛋白八聚體的結(jié)合，使核小體結(jié)構(gòu)變得緊密，阻止各種轉(zhuǎn)錄因子和輔助轉(zhuǎn)錄因子與DNA結(jié)合位點(diǎn)特異性結(jié)合，抑制基因表達(dá)。水稻OsSRT1是一個(gè)依賴NAD+的去乙?；?。該研究團(tuán)隊(duì)前期研究結(jié)果表明該基因下降表達(dá)會(huì)導(dǎo)致活性氧爆發(fā)和細(xì)胞死亡，超表達(dá)該基因后可以增強(qiáng)水稻對(duì)氧化脅迫的抗性（Huang et al., 2007）。這些研究結(jié)果表明OsSRT1參與植物細(xì)胞氧化還原狀態(tài)的調(diào)控。眾所周知，作為自養(yǎng)性的植物，其初級(jí)碳及能量代謝與動(dòng)物可能存在很大的差異。盡管前期的實(shí)驗(yàn)結(jié)果表明OsSRT1可以直接參與種子和幼苗中代謝相關(guān)基因的表觀調(diào)控（Zhong et al., 2013; Zhang et al., 2015）。但是OsSRT1是如何調(diào)控植物細(xì)胞中能量和代謝流的機(jī)制還不是十分清楚。

在本研究中，周道繡課題組通過遺傳學(xué)、分子生物學(xué)和生物化學(xué)等方法證明OsSRT1與水稻糖酵解中的關(guān)鍵限速酶3-磷酸甘油醛脫氫酶（GAPDH）相互作用，同是也發(fā)現(xiàn)3-磷酸甘油醛脫氫酶具有直接調(diào)控一系列糖酵解酶基因的轉(zhuǎn)錄激活功能。研究還發(fā)現(xiàn)，OsSRT1通過調(diào)節(jié)GAPDH的賴氨酸乙酰化水平對(duì)其轉(zhuǎn)錄活性、核質(zhì)中的比例進(jìn)行動(dòng)態(tài)調(diào)控，進(jìn)而影響水稻的能量代謝。

本論文的第一作者是來自生命科學(xué)技術(shù)學(xué)院理科基地班專業(yè)的張華博士，周道繡教授為該文的通訊作者，趙毓教授也是該文的共同作者。該研究得到了國家自然科學(xué)基金、國家重大研發(fā)計(jì)劃、111引智計(jì)劃、華中農(nóng)業(yè)大學(xué)校內(nèi)創(chuàng)新基金、中央高校基本科研業(yè)務(wù)費(fèi)專項(xiàng)基金和人才啟動(dòng)基金等的資助。

Sirtuins, a family of proteins with homology to the yeast silent information regulator 2 (Sir2), are NAD+-dependent histone deacetylases and play crucial roles in energy sensing and regulation in yeast and animal cells. Plants are autotrophic organisms and display distinct features of carbon and energy metabolism. It remains largely unexplored whether and how plant cells sense energy/redox status to control carbon metabolic flux under various growth conditions. In this work, we show that the rice nuclear sirtuin OsSRT1 not only functions as an epigenetic regulator to repress glycolytic genes expression and glycolysis in seedlings, but also inhibits transcriptional activity of glyceraldehyde-3-phosphatedehydrogenase (GAPDH) that is enriched on glycolytic genes promoters and stimulates their expression. We show that OsSRT1 reduces GAPDH lysine acetylation and nuclear accumulation that are enhanced by oxidative stress. Mass spectrometry identified six acetylated lysines regulated by OsSRT1. OsSRT1-dependent lysine deacetylation of OsGAPDH1 represses transcriptional activity of the protein. The results indicate that OsSRT1 represses glycolysis by both regulating epigenetic modification of histone and inhibiting the moonlighting function of GAPDH as a transcriptional activator of glycolytic genes in rice.

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