Bai, Hanzhong; (2024) Transcriptome-wide interrogation of protein-mediated RNA-RNA interactomes. Doctoral thesis (Ph.D), UCL (University College London).

Preview

Text Bai_10197532_thesis.pdf Download (50MB) | Preview

Abstract

Over the last decade, advances in transcriptomic methods have yielded detailed understanding of protein-RNA interactions and RNA structures that contribute both to transcriptional and post-transcriptional regulation. It has also become clear that RNA-binding proteins (RBPs) can simultaneously bind to distinct RNA molecules, or to distal parts of long RNAs, and thus bring them into proximity. Recently, a method termed “RNA in situ conformation sequencing (RIC-seq)” has been developed to study such protein-mediated transcriptome-wise RNA-RNA interactions (RRIs) by using proximity ligation to produce chimeric reads. I made a series of improvements in the experimental part of RIC-seq, and devised a comprehensive computational workflow to analyse chimeric RIC-seq reads. I then produced data to assess the roles of protein co-factors that are potentially involved in nuclear RNA-RNA interactions, with a focus on the nuclear matrix protein MATR3. Furthermore, I performed detailed characterisation of gene-level RRI changes upon MATR3 depletion using an inducible degradation system, and focused my analysis on RNAs derived from enhancers, which are genomic sequences facilitating transcription of cognate promoters and often transcribe short noncoding RNAs that are involved in gene regulation. The thesis thus provides novel insights into the roles of RNA topological interactions in gene regulation.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as JSONCSVXML

Downloads by country - last 12 months

Export as XMLJSONCSV

Archive Staff Only

View Item