A study of mRNA translation with computational analysis of ribosome profiling datasets

Abstract

Ribosome profiling is based on capturing and sequencing of the mRNA fragments enclosed within the translating ribosome and it thereby provides a “snapshot” of ribosome positions at the transcriptome wide level. The approach was developed in 2009 and was a significant advancement towards the better understanding of the regulation of protein synthesis. I this thesis I describe my analysis of ribosome profiling data. In Chapter 1, I present a review of the recent developments of understanding obtained with ribosome profiling as well as discussing the implications of artifacts on the interpretation of its data. Chapters 2 and 3 details using ribosome profiling to examine the translational response to eIF2 repression and to the deprivation of oxygen and glucose respectively. Chapter 4 details how the interaction of the Shine Dalgarno with the ribosome rRNA alters the length of the mRNA protected fragments. In Chapter 5, I present analysis at identifying the relative impact of mRNA features on local ribosome profiling read density.