捷克科学院有机化学和生物化学研究所Vaclav Veverka和美国贝勒医学院H. Courtney Hodges课题组合作取得新进展。他们提出一个普遍存在的无序蛋白质相互作用模块协调转录伸长。这一研究成果于2021年11月26日发表在国际顶尖学术期刊《科学》上。

他们确定了一个常见的二元交互模块，由TFIIS N端结构域 (TND) 和原生非结构化TND交互基序 (TIM) 组成。 该模块在延伸机制和连接复合物之间是保守的，包括转录因子 TFIIS、Mediator、超延伸复合物、elongin、IWS1、SPT6、PP1-PNUTS 磷酸酶、H3K36me3 阅读器和其他因子。

使用核磁共振、活细胞显微技术和质谱，他们揭示了这些相互作用的结构基础，并发现 TND-TIM 序列对于在拥挤的核环境中诱导强烈和特定的共定位是必要和足够的。 IWS1中单个TIM的破坏导致基因表达和RNA 聚合酶 II (RNAP2)延伸动力学的强烈变化，这强调了 TND-TIM 表面对转录延伸的功能重要性。

据了解，在真核转录延伸过程中，RNAP2受一系列因素的调控。

附：英文原文

Title: A ubiquitous disordered protein interaction module orchestrates transcription elongation

Author: Katerina Cermakova, Jonas Demeulemeester, Vanda Lux, Monika Nedomova, Seth R. Goldman, Eric A. Smith, Pavel Srb, Rozalie Hexnerova, Milan Fabry, Marcela Madlikova, Magdalena Horejsi, Jan De Rijck, Zeger Debyser, Karen Adelman, H. Courtney Hodges, Vaclav Veverka

Issue&Volume: 2021-11-26

Abstract: During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation complex, elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other factors. Using nuclear magnetic resonance, live-cell microscopy, and mass spectrometry, we revealed the structural basis for these interactions and found that TND-TIM sequences were necessary and sufficient to induce strong and specific colocalization in the crowded nuclear environment. Disruption of a single TIM in IWS1 induced robust changes in gene expression and RNAP2 elongation dynamics, which underscores the functional importance of TND-TIM surfaces for transcription elongation.

DOI: abe2913

Source: https://www.science.org/doi/10.1126/science.abe2913