转录机器:绳上舞者  

Transcription apparatus:A dancer on a rope

作　　者：王耀来 刘锋[2] Wang Yaolai;Liu Feng(School of Science,Jiangnan University,Wuxi 214122,China;Department of Physics,Nanjing University,Nanjing 210093,China)

机构地区：[1]江南大学理学院,无锡214122 [2]南京大学物理系,南京210093

出　　处：《物理学报》2020年第24期1-12,共12页Acta Physica Sinica

基　　金：国家自然科学基金(批准号:11804123,11831015,11874209)资助的课题.

摘　　要：转录机器是响应细胞信号并启动基因转录的分子机器.它控制着基因在恰当的时间以适当的速率表达,演奏着生命之曲的底层旋律.为了揭示转录机器的工作原理,研究人员从其结构、动力学、信号转导等不同的维度进行探索.研究进程在跌宕起伏中螺旋式上升,各大研究领域趋于成熟却也趋于独立.故此,本文着眼全局,扼要介绍真核生物转录机器在多领域的重要进展,着重呈现看似大相径庭的新发现.结构研究揭示了转录机器的基本架构,核心争议在于媒介子(也称中介体复合物)的信号传递方式—“变构效应”抑或“招募导引”.超级增强子的可能工作机制包括令人遐想的“液相分离”和“精确协作”.“转录钟”研究揭示了转录动力学的基本特征.转录爆发现象的发现,带来了转录调控机制的“调频”与“调幅”之争—前者得到了更多的支持.此外,本文也概述了转录研究的技术困难和理论模型,提供了基于系综统计方法的研究策略,并介绍了转录机器的理想模型.转录机器在DNA上的运转方式源自进化的长河,似乎是对物理学定律的完美运用与平衡.Laws of physics govern all forms of matter movement.However,lives,which are composed of chemical elements which everyone is familiar with,are largely beyond physical description available.This is because the construction of life is not the same as that of general matters,rendering it unknown how physics laws are utilized.In this paper,we present our thinking on the transcriptional apparatus(TA).The TA is a huge molecular machine acting to sense regulatory signals and initiate transcripts at right time and with right rate.The operation of the TA is fundamental to almost all forms of lives.Although great progress has been made in recent years,one often has to face contradictory conclusions from different studies.Additionally,the studies of transcription are divided into several fields,and different fields are increasingly separate and independent.Focusing on eukaryotic transcription,in this review we briefly describe major advances in various fields and present new conflicting view points.Although the structural studies have revealed the main components and architecture of the TA,it is still unclear how the Mediator complex transmits signals from activators to the core transcriptional machinery at the promoter.It is believed that the Mediator functions to recruit RNA polymerase II onto the promoter and promote the entry into transcriptional elongation,which fails to explain how the signal transduction is achieved.On the other hand,the allostery effect of the Mediator allows for signal transmission but is not supported by structural study.It is reported that enhancers,especially supper enhancers,act to recruit activators via forming a so-called liquid drop and phase separation.By contrast,it is suggested that enhancers should cooperate delicately to orchestrate transcription.Results on the kinetics of protein-promoter interaction also contrast with each other,leading to a paradox called“transcriptional clock”.It is then concluded that proteins interact frequently and transiently with promoters and different prot

关 键 词：分子结构 信号转导 随机过程 生命现象 

分 类 号：Q753[生物学—分子生物学]