Bioinformatical analysis of RNA - protein interactions in AU-rich element mediated decay
This work is concerned with the interaction of RNA binding proteins (RPBs) and their RNA target sites. The main focus lies on proteins interacting with AU-rich elements (AREs), so called AU-rich binding proteins (ABPs). Their targets, AREs, are cis-acting RNA motifs found throughout genes in many higher organisms. Their function in AU- rich element mediated decay and the factors discriminating between active (bound) and inactive (unbound) status of such RNA elements is subject to this study. We
... analyzed PAR-iCLIP data, identifying main targets of tristetrapro- lin (TTP) and HuR (ELAVL1) in LPS induced, primary bonemarrow derived marcophages (BMDMs) in mouse. The influence of RNA sec- ondary structure on binding, cooperative vs. competitive behavior of RBPs, correlation with mRNA decay rates, over-represented binding motifs and differences between early and late immune-response bind- ing of TTP are part of this thesis. Furthermore, we compare our dataset to an over-expression study and investigate the potential of our predictions in mouse for their portability to human. Our previously published database for AREs in human and mouse (AREsite) was updated during this thesis and replaced by a new version (AREsite2), which contains annotations of AU-/GU- and U-rich elements in all genic regions (exons, introns, UTRs) of coding and non-coding genes in human, mouse, fruit fly, zebrafish and bandworm. Together with an example analysis of AREsite2 derived data, this the- sis presents a comprehensive analysis of RNA elements and their se- quence and structure features crucial for functional RNA-RBP inter- action.