近日，華中農(nóng)業(yè)大學(xué)作物遺傳改良國(guó)家重點(diǎn)實(shí)驗(yàn)室周道繡課題組首次在真核生物中報(bào)道了組蛋白去乙酰化酶對(duì)核糖體蛋白乙?；揎椀恼{(diào)控及其功能的影響。該研究將蛋白的賴氨酸乙?；揎椪{(diào)控從轉(zhuǎn)錄水平擴(kuò)展到蛋白質(zhì)翻譯水平，拓展和深化了人們對(duì)于表觀調(diào)控機(jī)制的認(rèn)知。
細(xì)胞中蛋白質(zhì)功能的精細(xì)調(diào)控對(duì)于生物生長(zhǎng)和發(fā)育至關(guān)重要，其中蛋白質(zhì)的乙?；?、磷酸化等翻譯后修飾是一種可逆、迅速且經(jīng)濟(jì)節(jié)約的調(diào)控方式。賴氨酸乙?；↘ac）是一種以乙酰輔酶A為供體的蛋白質(zhì)翻譯后修飾。華中農(nóng)業(yè)大學(xué)作物遺傳改良國(guó)家重點(diǎn)實(shí)驗(yàn)室周道繡課題組基于質(zhì)譜的蛋白質(zhì)組學(xué)數(shù)據(jù)發(fā)現(xiàn)，乙酰化修飾不僅僅發(fā)生在組蛋白上，而且也廣泛存在于細(xì)胞質(zhì)中具有多種功能的代謝酶、轉(zhuǎn)錄因子及核糖體蛋白等非組蛋白上。該課題組之前解析了組蛋白去乙?；福℉istone deacetylase， HDAC）特異去除細(xì)胞質(zhì)代謝酶和轉(zhuǎn)錄因子乙酰化修飾的作用機(jī)制。然而，核糖體蛋白是否也受組蛋白（去）乙酰化酶的調(diào)控以及乙?；揎棇?duì)核糖體蛋白的調(diào)控功能還不是十分清楚。
圖1. HDAC對(duì)組蛋白以及核糖體蛋白乙?；揎椀恼{(diào)控
本研究中，作者首先對(duì)水稻中3個(gè)細(xì)胞質(zhì)定位的組蛋白去乙酰化酶HDA705、 HDA706和 HDA714突變體進(jìn)行了全蛋白組乙?；揎椬V定量分析，發(fā)現(xiàn)組蛋白去乙?；窰DA714是水稻非組蛋白乙?；闹饕{(diào)控因子，該基因突變后導(dǎo)致大量非組蛋白乙?；揎椝缴仙?，其中包括參與翻譯過(guò)程的核糖體蛋白及翻譯因子。
乙酰輔酶A不僅僅是乙?；傅牡孜?，而且也是非常重要的中間能量代謝產(chǎn)物，蛋白質(zhì)乙?；赡芊磻?yīng)了細(xì)胞內(nèi)能量代謝水平。HDAC調(diào)控的組蛋白代謝和核糖體乙酰化揭示了植物蛋白能量代謝在協(xié)調(diào)基因表達(dá)和翻譯中的功能。生化實(shí)驗(yàn)進(jìn)一步表明水稻組蛋白去乙?；窰DA714可以特異地去除核糖體蛋白賴氨酸上的乙?；揎棥?/div>
hda714翻譯組學(xué)分析表明核糖體蛋白的乙?；揎椏梢源龠M(jìn)核糖體與mRNA的結(jié)合，對(duì)蛋白的翻譯效率進(jìn)行調(diào)控。該研究將蛋白的賴氨酸乙酰化修飾調(diào)控從轉(zhuǎn)錄水平擴(kuò)展到蛋白質(zhì)翻譯水平，拓展和深化了人們對(duì)于表觀調(diào)控機(jī)制的認(rèn)知，對(duì)非組蛋白乙酰化功能的后續(xù)研究具有指導(dǎo)意義。
【英文摘要】
Lysine acetylation （Kac） is well known to occur in histones for chromatin function and epigenetic regulation. In addition to histones, Kac is also detected in a large number of proteins with diverse biological functions. However, Kac function and regulatory mechanism for most proteins are unclear. In this work, we studied mutation effects of rice genes encoding cytoplasm-localized histone deacetylases （HDAC） on protein acetylome and found that the HDAC protein HDA714 was a major deacetylase of the rice non-histone proteins including many ribosomal proteins （r-proteins） and translation factors that were extensively acetylated. HDA714 loss-of-function mutations increased Kac levels but reduced abundance of r-proteins. In vitro and in vivo experiments showed that HDA714 interacted with r-proteins and reduced their Kac. Substitutions of lysine by arginine （depleting Kac） in several r-proteins enhance, while mutations of lysine to glutamine （mimicking Kac） decrease their stability in transient expression system. Ribo-seq analysis revealed that the hda714 mutations resulted in increased ribosome stalling frequency. Collectively, the results uncover Kac as a functional posttranslational modification of r-proteins which is controlled by histone deacetylases, extending the role of Kac in gene expression to protein translational regulation.
論文鏈接：
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkab244/6219121?searchresult=1#234917398
日期：2021-04-13
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