近日，華中農(nóng)業(yè)大學(xué)作物遺傳改良國家重點實驗室周道繡課題組首次在真核生物中報道了組蛋白去乙?；笇颂求w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)錄水平擴展到蛋白質(zhì)翻譯水平，拓展和深化了人們對于表觀調(diào)控機制的認(rèn)知。
細(xì)胞中蛋白質(zhì)功能的精細(xì)調(diào)控對于生物生長和發(fā)育至關(guān)重要，其中蛋白質(zhì)的乙酰化、磷酸化等翻譯后修飾是一種可逆、迅速且經(jīng)濟節(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)作物遺傳改良國家重點實驗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?；揎椀淖饔脵C制。然而，核糖體蛋白是否也受組蛋白（去）乙?；傅恼{(diào)控以及乙?；揎棇颂求w蛋白的調(diào)控功能還不是十分清楚。
圖1. HDAC對組蛋白以及核糖體蛋白乙酰化修飾的調(diào)控
本研究中，作者首先對水稻中3個細(xì)胞質(zhì)定位的組蛋白去乙酰化酶HDA705、 HDA706和 HDA714突變體進行了全蛋白組乙?；揎椬V定量分析，發(fā)現(xiàn)組蛋白去乙?；窰DA714是水稻非組蛋白乙酰化的主要調(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?；傅牡孜铮乙彩欠浅Ｖ匾闹虚g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。生化實驗進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?。
hda714翻譯組學(xué)分析表明核糖體蛋白的乙?；揎椏梢源龠M核糖體與mRNA的結(jié)合，對蛋白的翻譯效率進行調(diào)控。該研究將蛋白的賴氨酸乙?；揎椪{(diào)控從轉(zhuǎn)錄水平擴展到蛋白質(zhì)翻譯水平，拓展和深化了人們對于表觀調(diào)控機制的認(rèn)知，對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
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