生物大分子相分离及其在转录调控中的功能  

Phase Separation of Biomacromolecules and Its Important Role in Transcriptional Regulation

作　　者：赵相东 王乐 马卢杰 谢德宝 高梦迪 孟亚南 曾凡力 ZHAO Xiang-Dong;WANG Le;MA Lu-Jie;XIE De-Bao;GAO Meng-Di;MENG Ya-Nan;ZENG Fan-Li(College of Life Sciences,Hebei Agricultural University,Baoding 071001,China)

机构地区：[1]河北农业大学生命科学学院,保定071001

出　　处：《生物化学与生物物理进展》2024年第4期743-753,共11页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(32070574);河北省杰出青年自然科学基金(C2023204155)资助项目。

摘　　要：相分离(phase separation)是包括蛋白质、核酸在内的生物大分子形成凝聚体或无膜细胞器(membraneless organelles,MLOs)的基本组织原理。已发现生物大分子发生相分离需要一些典型的内在特征条件,如无序区域、模块化结构域、多价相互作用等。生物大分子相分离在许多重要细胞活动中发挥关键功能,近年来基因转录调控中生物大分子相分离成为研究热点。RNA聚合酶、转录因子(transcription factors,TFs)、超级增强子(super enhancers,SEs)等转录调控元件都通过相分离发挥重要作用。而且转录调控过程中的相分离与癌症发生密切相关。本文就生物大分子相分离形成的内在特征条件和相分离在转录调控中的重要作用进行综述,为理解基本细胞活动和癌症中的基因调控提供参考。Cells not only contain membrane-bound organelles(MBOs),but also membraneless organelles(MLOs)formed by condensation of many biomacromolecules.Examples include RNA-protein granules such as nucleoli and PML nuclear bodies(PML-NBs)in the nucleus,as well as stress granules and P-bodies in the cytoplasm.Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles(MLOs)of biomacromolecules including proteins and nucleic acids.In particular,liquid-liquid phase separation(LLPS)compartmentalises and concentrates biological macromolecules into liquid condensates.It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics,such as intrinsically disordered regions,modular domains and multivalent interactions.The phase separation of biomacromolecules plays a key role in many important cell activities.In recent years,the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation.Transcriptional regulatory elements such as RNA polymerases,transcription factors(TFs),and super enhancers(SEs)all play important roles through phase separation.Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II(RNAPII)subunits in the cytoplasm,and this process is reversible,suggesting a novel regulatory model of eukaryotic transcription machinery.The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs.Moreover,phase separation during transcriptional regulation is closely related to the occurrence of cancer.For example,the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs.In this review,the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional re

关 键 词：无膜细胞器 相分离 转录调控 生物大分子 癌症 

分 类 号：Q7[生物学—分子生物学]