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(jìn)行了全蛋白組乙酰化修飾譜定量分析，發(fā)現(xiàn)組蛋白去乙酰化酶HDA714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)致大量非組蛋白乙酰化修飾水平上升，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不僅僅是乙酰化酶的底物，而且也是非常重要的中間能量代謝產(chǎn)物，蛋白質(zhì)乙酰化可能反應(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酰化酶HDA714可以特異地去除核糖體蛋白賴氨酸上的乙酰化修飾。

 

　　hda714翻譯組學(xué)分析表明核糖體蛋白的乙酰化修飾可以促進(jìn)核糖體與mRNA的結(jié)合，對蛋白的翻譯效率進(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于表觀調(diào)控機(jī)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