RNA Nuclear Export: From Neurological Disorders to Cancer
RNA Nuclear Export: From Neurological Disorders to Cancer
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DOI：
10.1007/978-3-319-60733-7_6
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Hautbergue, Guillaume M.
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文献类型：
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作者：
Hautbergue, Guillaume M.
核膜的存在定义了所有真核细胞的结构框架，它将含有遗传物质的细胞核与进行蛋白质合成的细胞质分开。因此，真核生物中蛋白质的翻译依赖于DNA编码的RNA分子通过嵌入核膜的小孔的主动运输。这一过程涉及几种机制，通常被称为RNA核输出或核质运输。基因的调控表达需要蛋白质编码信使RNA分子(MRNAs)和非编码RNA(NcRNAs)以及蛋白质和预组装的核糖体亚基的核输出。MRNAs的核输出与RNA聚合酶II合成的新生转录物的共转录加工有内在联系。这种功能偶联对于细胞的生存至关重要，允许完全加工的转录物及时核输出，否则可能导致异常蛋白质的翻译，如一些神经退行性疾病中产生的聚合重复蛋白。核输出途径的改变也可能导致基因组的不稳定和各种形式的癌症。本章将描述驱动RNA核出口的分子机制，并特别强调mRNAs。它还将审查他们在神经疾病和癌症方面的已知变化，以及他们最近为潜在开发新的治疗策略提供的机会。
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.