Dynamic modules of the coactivator SAGA in eukaryotic transcription.
Dynamic modules of the coactivator SAGA in eukaryotic transcription.
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DOI：
10.1038/s12276-020-0463-4
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发表时间：
2020-07
影响因子：
12.8
通讯作者：
Lee D
中科院分区：
文献类型：
--
作者：
Cheon Y;Kim H;Park K;Kim M;Lee D
SAGA(SPT-Ada-Gcn5乙酰转移酶)是一个高度保守的转录共激活因子，由四个功能独立的模块组成。它的两种不同的酶活性，组蛋白乙酰化和去泛素化，在染色质上建立了特定的表观遗传模式，从而调节基因的表达。虽然早期的研究强调了SAGA在调控全球转录中的重要性，但最近的报道表明，SAGA参与了基因表达的其他方面，因此在整个过程中发挥着更全面的调节作用。在这里，我们讨论了最近对每个SAGA模块的结构和功能的研究，并将SAGA的亚基组成与酵母和后生动物中的相关复合体进行了比较。我们讨论了SAGA去泛素化模块(DUBm)在mRNA监测和输出，以及在转录起始和延伸中的调节作用。这一发现表明，SAGA在转录的多个阶段中扮演着多种角色。此外，我们还描述了SAGA与人类疾病的关系。总体而言，在这份报告中，我们说明了对SAGA在转录调控和微调基因表达的疾病含义方面的新揭示的理解。一种有助于向基因组添加表观遗传信息的蛋白质SAGA控制着基因激活的许多方面，可能使其成为癌症治疗的靶点。为了适应微小的细胞核，基因组被紧紧地打包在一起，基因必须在被激活之前被解开。众所周知，SAGA在基因组开放中很重要，现在已经被证明在基因激活中也扮演着许多角色。韩国大田KAIST的Daeyoup Lee和他的同事回顾了关于佐贺的结构、功能和在疾病中的作用的最新发现。他们报告说，SAGA的复合体(19个亚基被组织成四个模块)使其能够发挥如此多的作用，基因组打开，启动转录，并有效地输出mRNA。它的主人角色意味着SAGA的故障可能与许多疾病有关。
SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved transcriptional coactivator that consists of four functionally independent modules. Its two distinct enzymatic activities, histone acetylation and deubiquitylation, establish specific epigenetic patterns on chromatin and thereby regulate gene expression. Whereas earlier studies emphasized the importance of SAGA in regulating global transcription, more recent reports have indicated that SAGA is involved in other aspects of gene expression and thus plays a more comprehensive role in regulating the overall process. Here, we discuss recent structural and functional studies of each SAGA module and compare the subunit compositions of SAGA with related complexes in yeast and metazoans. We discuss the regulatory role of the SAGA deubiquitylating module (DUBm) in mRNA surveillance and export, and in transcription initiation and elongation. The findings suggest that SAGA plays numerous roles in multiple stages of transcription. Further, we describe how SAGA is related to human disease. Overall, in this report, we illustrate the newly revealed understanding of SAGA in transcription regulation and disease implications for fine-tuning gene expression. A protein that helps add epigenetic information to genome, SAGA, controls many aspects of gene activation, potentially making it a target for cancer therapies. To fit inside the tiny cell nucleus, the genome is tightly packaged, and genes must be unpacked before they can be activated. Known to be important in genome opening, SAGA has now been shown to also play many roles in gene activation. Daeyoup Lee at the KAIST, Daejeon, South Korea, and co-workers have reviewed recent discoveries about SAGA’s structure, function, and roles in disease. They report that SAGA’s complex (19 subunits organized into four modules) allows it to play so many roles, genome opening, initiating transcription, and efficiently exporting mRNAs. Its master role means that malfunction of SAGA may be linked to many diseases.
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