Investigating the links between the nuclear RNA exosome and RNA export in fission yeast

Thesis

Production of the correct amount of functional RNA molecules is vital for cell survival. This can be achieved at different times during the life of an RNA molecule, starting with RNA synthesis and ending at RNA degradation, whilst passing through maturation and transport inside the cell. In eukaryotes, an important player in RNA regulation is the essential multi-protein 3’ to 5’ RNA exosome complex. This molecular scissor monitors the correct maturation and levels of a diverse variety of protein-coding and non-coding RNA transcripts as well as plays a role in the export of RNAs from the nucleus to the cytoplasm. However, the molecular mechanism underpinning various functions of the exosome in RNA regulation are not well understood. The work presented here explores the possible links between a predicted export protein Sbp1, component of Ran GTPase complex and the nuclear RNA exosome. This study characterises Sbp1 and links Sbp1 to Dis3, the main catalytic RNase of the exosome, accentuating the relation between RNA export and decay. Secondly, this study uses the data collected from the poly(A)+ interactome to investigate possible mechanisms involved in substrate recognition by the nuclear RNA exosome. These results propose a two-step mechanism of RNA substrate recognition in which a specific ribonucleoparticle is assembled and then targeted by the nuclear exosome, which is coordinated by the essential helicase Mtl1/Mtr4.

Authors: Priest, E

• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Subjects: RNA; RNA decay; RNA exosome