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RNA Nuclear Export: From Neurological Disorders to Cancer

  • Guillaume M. HautbergueEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1007)

Abstract

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.

Keywords

RNA Nuclear export Nuclear Pore Complex (NPC) TREX complex NXF1 Exportins Neurodegenerative diseases Cancer 

Notes

Acknowledgments

G.M.H. acknowledges support from the Motor Neurone Disease Association (grant Apr16/846-791), the Medical Research Council (MRC grant MR/M010864/1) and the Thierry Latran Foundation (grant FTLAAP2016/Astrocyte secretome).

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Copyright information

© American Association of Pharmaceutical Scientists 2017

Authors and Affiliations

  1. 1.RNA Biology Laboratory, Sheffield Institute for Translational Neuroscience (SITraN), Department of NeuroscienceUniversity of SheffieldSheffieldUK

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