RNA出核转运及其调控  

Mechanism and regulation of RNA nuclear export

作　　者：陈冠霖 范静 程红 CHEN Guanlin;FAN Jing;CHENG Hong(Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,Shanghai 200031,China;School of Life Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China)

机构地区：[1]中国科学院分子细胞科学卓越创新中心,上海200031 [2]国科大杭州高等研究院生命与健康科学学院,中国科学院大学,杭州310024

出　　处：《生命的化学》2024年第9期1524-1541,共18页Chemistry of Life

基　　金：国家重点基础研究发展计划项目(2022YFA1303300);国家自然科学基金项目(31925008,32230022);中国科学院战略性先导科技专项项目(XDB0570100)。

摘　　要：生物体中遗传信息的传递遵循中心法则,即从基因组DNA传递到RNA,再进一步传递到蛋白质。作为遗传信息传递的中间一环,RNA需要在细胞核中生成,并进一步被转运到细胞质中,其中涉及的RNA出核转运过程则是保证遗传信息精确传递的重要步骤,并参与了基因表达的精确调控过程。绝大多数的mRNA通常在细胞核内包装形成mRNP,并在TREX复合体(transcription-export complex,TREX)和出核因子NXF1(nuclear RNA export factor 1)的帮助下转运出核。另有一小部分的mRNA则以CRM1(chromosome region maintenance protein 1)依赖的方式进行出核转运。大量研究表明,mRNA出核过程不仅与上游的转录和加工相偶联,而且能够反向调控上游步骤。此外,细胞核中RNA的出核机器与降解机器相互竞争,共同决定新生RNA的核内命运。尤为重要的是,当mRNA出核受阻时,在细胞和个体层面上会产生不同程度的生理或病理缺陷。最新的研究表明,除mRNA以外,circRNA和lncRNA等其他RNA分子也被认为能够转运出核并翻译产生蛋白质,参与各类生物学过程的调控,其出核过程则涉及一些新的受体因子和调控蛋白。本文将结合最新的研究进展,对已知RNA出核转运通路的相关具体过程和调控机制进行总结,并对领域内后续研究的重难点进行讨论和展望。The transmission of genetic information in organisms usually follows the genetic central dogma,which means the genetic information transfers from genomic DNA to RNA,and then further to protein.As an intermediate link in this transmission,RNA molecules need to be generated in the nucleus and further transported to the cytoplasm.So RNA nuclear export is a key step to ensure the correct transmission of genetic information and the precise regulation of gene expression.The majority of mRNAs are usually packaged to mRNPs in nucleus,which are exported by transcription-export complex(TREX)and nuclear RNA export factor 1(NXF1).Meanwhile,a small portion of mRNAs are exported in a chromosome region maintenance protein 1(CRMI)-dependent manner.Numerous studies have shown that mRNA nuclear export is not only coupled to upstream transcription and processing,but also as a new pathway to regulate upstream mRNA processes.Additionally,the RNA nuclear export machinery competes with the degradation machinery and determines nascent mRNAs fate.More importantly,blocking mRNA nuclear export can produce varying degrees of physiological or pathological defects at cellular and animal levels.According to latest research,other RNA molecules like circRNA and lncRNA,which have been found to be exported to cytoplasm and regulated different biological processes by producing proteins through translation,are exported by utilizing several new receptors and adaptors.In this review,we will summarize the known RNA nuclear export pathways about their specific mechanisms and regulations by following the latest scientific progresses,and highlight the key points of subsequent research in related field.

关 键 词：RNA出核转运 TREX复合体 NXF1 mRNP包装 核质运输 

分 类 号：Q752[生物学—分子生物学]