Mechanisms controlling mRNA processing and translation: decoding the regulatory layers defining gene expression through RNA sequencing

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Mechanisms controlling mRNA processing and translation: decoding the regulatory layers defining gene expression through RNA sequencing

Type: Doctoral Thesis
Title: Mechanisms controlling mRNA processing and translation: decoding the regulatory layers defining gene expression through RNA sequencing
Author: Klerk, Eleonora de
Publisher: Department of Human Genetics, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2015-09-30
Keywords: RNA sequencing
Gene expression
mRNA
Gene regulation
Post-transcriptional control
Alternative polyadenylation
Translation
Abstract: The work described in this thesis focuses on the mechanisms that give rise to alternative mRNAs and their alternative translation into proteins. Each of the described studies has been based on a specific set of high-throughput RNA sequencing technologies. An overview of the available RNA sequencing methods, together with an introduction to different regulatory layers which define the expression of a gene, are presented in Chapter 1. Our work in Chapter 2 and Chapter 3 investigates the process of alternative polyadenylation. Chapter 2 shows the role of alternative polyadenylation in the context of oculopharyngeal muscular dystrophy. Chapter 3 describes genetic variants associated with alternative polyadenylation. Chapter 4 focuses on mechanisms controlling protein synthesis (translation) during skeletal muscle differentiation, highlighting changes in the use of alternative translation initiation sites. In Chapter 5 we investigated the interdependence between alternative regulatory events in gene expression. In this study, based on single-molecule full-length RNA sequencing, we demonstrated coordination and interdependence between alternative transcription initiation, alternative splicing, and alternative polyadenylation. Finally, Chapter 6 connects fundamental research in the RNA field with clinical care, describing new diagnostic and therapeutic approaches.
Description: Promotor: J.T. den Dunnen, Co-Promotor: P.A.C. 't Hoen
With Summary in Dutch
Faculty: LUMC
Citation: Klerk, E. de, 2015, Doctoral Thesis, Leiden University
ISBN: 9789461825933
Handle: http://hdl.handle.net/1887/35768
 

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application/pdf Summary in English 202.8Kb View/Open
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