Hautbergue Guillaume M
RNA Biology Laboratory, Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK.
Adv Exp Med Biol. 2017;1007:89-109. doi: 10.1007/978-3-319-60733-7_6.
The presence of a nuclear envelope, also known as nuclear membrane, defines the structural framework of all eukaryotic cells by separating the nucleus, which contains the genetic material, from the cytoplasm where the synthesis of proteins takes place. Translation of proteins in Eukaryotes is thus dependent on the active transport of DNA-encoded RNA molecules through pores embedded within the nuclear membrane. Several mechanisms are involved in this process generally referred to as RNA nuclear export or nucleocytoplasmic transport of RNA. The regulated expression of genes requires the nuclear export of protein-coding messenger RNA molecules (mRNAs) as well as non-coding RNAs (ncRNAs) together with proteins and pre-assembled ribosomal subunits. The nuclear export of mRNAs is intrinsically linked to the co-transcriptional processing of nascent transcripts synthesized by the RNA polymerase II. This functional coupling is essential for the survival of cells allowing for timely nuclear export of fully processed transcripts, which could otherwise cause the translation of abnormal proteins such as the polymeric repeat proteins produced in some neurodegenerative diseases. Alterations of the mRNA nuclear export pathways can also lead to genome instability and to various forms of cancer. This chapter will describe the molecular mechanisms driving the nuclear export of RNAs with a particular emphasis on mRNAs. It will also review their known alterations in neurological disorders and cancer, and the recent opportunities they offer for the potential development of novel therapeutic strategies.
核膜（也称为核被膜）的存在通过将包含遗传物质的细胞核与进行蛋白质合成的细胞质分隔开来，定义了所有真核细胞的结构框架。因此，真核生物中的蛋白质翻译依赖于DNA编码的RNA分子通过嵌入核膜的孔进行主动运输。该过程涉及多种机制，通常称为RNA核输出或RNA的核质运输。基因的调控表达需要蛋白质编码信使RNA分子（mRNA）以及非编码RNA（ncRNA）与蛋白质和预先组装的核糖体亚基一起进行核输出。mRNA的核输出与RNA聚合酶II合成的新生转录本的共转录加工内在相关。这种功能偶联对于细胞的存活至关重要，它允许完全加工的转录本及时进行核输出，否则可能导致异常蛋白质的翻译，例如某些神经退行性疾病中产生的聚合重复蛋白。mRNA核输出途径的改变也可能导致基因组不稳定和各种形式的癌症。本章将描述驱动RNA核输出的分子机制，特别强调mRNA。还将综述它们在神经疾病和癌症中的已知改变，以及它们最近为新型治疗策略的潜在发展提供的机会。
