In the Footsteps of the Rugged Trail of Transcription
In de voetstappen van het ruige pad van transcriptie
This thesis explores multiple aspects of the transcription regulatory network with regards to human cells - From the initiation of transcription to the efficiency of translation.
Chapter 2 attempts to establish a connection between the transcription and translation processes. By employing multiple in vitro experiments, a positive correlation between transcription and translation was first discovered, where it was solely controlled via transcription rate. The study leads to the identification of one of the first known functions of m6A at coding regions. While seemingly counterintuitive to the current recognition about m6A on translation, we augment the role of m6A on translation via the discovery of its co-transcriptional deposition.
Chapter 3 reviews the connection between the transcription steps of splicing, export, decay, and translation of mRNA, reinforcing the hypothesis that transcription is not an independent event, and is instead linked to the entire life cycle of mRNA.
Chapter 4 investigates the functional role of AP1 in enhancer regions during OIS. The study results in the identification of a novel enhancer with an AP1 binding motif regulating senescence through its target gene FOXF1. Although extensively characterized, AP1 and FOXF1 are not reported to act as regulators of senescence. A new trans-regulatory network of genes to counterbalance the effect of oncogene activation was uncovered.
In Chapter 5, a general discussion about the current view of the field is conducted.
Finally, some outlooks are raised to potentially generate a better understanding of transcriptional regulation.
|Keywords||Transcription, translation, RNA, epigenetics, gene regulation, enhancer, promoter, CRISPR, screen|
|Promotor||R. Agami (Reuven) , B. Slobodin (Boris)|
|Publisher||Erasmus University Rotterdam|
Han, R. (2019, February 14). In the Footsteps of the Rugged Trail of Transcription. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/115044