García-Oliver Encar, García-Molinero Varinia, Rodríguez-Navarro Susana
Centro de Investigación Príncipe Felipe (CIPF), Gene Expression coupled with RNA Transport Laboratory, Valencia, Spain.
Biochim Biophys Acta. 2012 Jun;1819(6):555-65. doi: 10.1016/j.bbagrm.2011.11.011. Epub 2011 Dec 8.
In the gene expression field, different steps have been traditionally viewed as discrete and unconnected events. Nowadays, genetic and functional studies support the model of a coupled network of physical and functional connections to carry out mRNA biogenesis. Gene expression is a coordinated process that comprises different linked steps like transcription, RNA processing, export to the cytoplasm, translation and degradation of mRNAs. Its regulation is essential for cellular survival and can occur at many different levels. Transcription is the central function that occurs in the nucleus, and RNAPII plays an essential role in mRNA biogenesis. During transcription, nascent mRNA is associated with the mRNA-binding proteins involved in processing and export of the mRNA particle. Cells have developed a network of multi-protein complexes whose functions regulate the different factors involved both temporally and spatially. This coupling mechanism acts as a quality control to solve some of the organization problems of gene expression in vivo, where all the factors implicated ensure that mRNAs are ready to be exported and translated. In this review, we focus on the functional coupling of gene transcription and mRNA export, and place particular emphasis on the relationship between the NPC-associated complex, TREX2, and the transcription co-activator, SAGA. We have pinpointed the experimental evidence for Sus1's roles in transcription initiation, transcription elongation and mRNA export. In addition, we have reviewed other NPC-related processes such as gene gating to the nuclear envelope, the chromatin structure and the cellular context in which these processes take place. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.
在基因表达领域,传统上不同步骤被视为离散且无关联的事件。如今,遗传学和功能研究支持了一个由物理和功能连接组成的耦合网络模型来进行mRNA生物合成。基因表达是一个协调的过程,包括转录、RNA加工、输出到细胞质、翻译以及mRNA降解等不同的关联步骤。其调控对细胞存活至关重要,且可在许多不同层面发生。转录是发生在细胞核中的核心功能,RNA聚合酶II在mRNA生物合成中起关键作用。在转录过程中,新生mRNA与参与mRNA颗粒加工和输出的mRNA结合蛋白相关联。细胞已形成一个多蛋白复合物网络,其功能在时间和空间上调控不同的因子。这种耦合机制作为一种质量控制手段,以解决体内基因表达的一些组织问题,其中所有相关因子确保mRNA准备好被输出和翻译。在本综述中,我们聚焦于基因转录与mRNA输出的功能耦合,尤其强调与核孔复合体相关的复合物TREX2和转录共激活因子SAGA之间的关系。我们已明确了Sus1在转录起始、转录延伸和mRNA输出中作用的实验证据。此外,我们还综述了其他与核孔复合体相关的过程,如基因与核膜的门控、染色质结构以及这些过程发生的细胞环境。本文是名为“核运输与RNA加工”的特刊的一部分。