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Clr4SUV39H1 ubiquitination and non-coding RNA mediate transcriptional silencing via heterochromatic phase transitions
bioRxiv - Molecular Biology Pub Date : 2023-09-21 , DOI: 10.1101/2021.01.08.425919
Hyun-Soo Kim , Benjamin Roche , Sonali Bhattacharjee , Leila Todeschini , An-Yun Chang , Chris Hammell , André Verdel , Robert A. Martienssen

Transcriptional silencing by RNAi paradoxically relies on transcription, but how the transition from transcription to silencing is achieved has remained unclear. The Cryptic Loci Regulator complex (CLRC) in Schizosaccharomyces pombe is a cullin-ring E3 ligase required for silencing that is recruited by RNAi. We found that the E2 ubiquitin conjugating enzyme Ubc4 interacts with CLRC and mono-ubiquitinates the histone H3K9 methyltransferase Clr4SUV39H1, promoting the transition from co-transcriptional gene silencing (H3K9me2) to transcriptional gene silencing (H3K9me3). Ubiquitination of Clr4 occurs in an intrinsically disordered region (IDR), which undergoes robust liquid-liquid phase separation (LLPS), along with Swi6HP1 the effector of transcriptional gene silencing. Phase separation of Clr4 and Swi6 is exquisitely sensitive to non-coding RNA (ncRNA), which promotes dimerization, chromatin association, and di-, but not tri- methylation instead. Ubc4-CLRC also targets the transcriptional co-activator Bdf2BRD4, down-regulating centromeric transcription and small RNA production. The deubiquitinase Ubp3 counteracts both activities.

中文翻译:

Clr4SUV39H1 泛素化和非编码 RNA 通过异染色质相变介导转录沉默

RNAi 引起的转录沉默矛盾地依赖于转录,但如何实现从转录到沉默的转变仍不清楚。粟酒裂殖酵母中的隐秘位点调节复合物 (CLRC)是沉默所需的库林环 E3 连接酶,由 RNAi 招募。我们发现E2泛素结合酶Ubc4与CLRC相互作用,单泛素化组蛋白H3K9甲基转移酶Clr4 SUV39H1,促进从共转录基因沉默(H3K9me2)到转录基因沉默(H3K9me3)的转变。Clr4 泛素化发生在本质无序区域 (IDR),该区域与 Swi6 HP1一起经历强大的液-液相分离 (LLPS)转录基因沉默的效应子。Clr4 和 Swi6 的相分离对非编码 RNA (ncRNA) 非常敏感,它会促进二聚化、染色质缔合和二甲基化,但不会促进三甲基化。Ubc4-CLRC 还靶向转录共激活因子 Bdf2 BRD4,下调着丝粒转录和小 RNA 的产生。去泛素酶 Ubp3 可以抵消这两种活性。
更新日期:2023-09-22
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