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Borislava Tsanova

Advisor: Ambro van Hoof, Ph.D.

Accepted position of Drug Safety Specialist at Pharmaceutical Product Development (PPD) in Sophia, Bulgaria after receiving PhD

The exosome is an essential complex of ten proteins involved in the processing and degradation of many RNAs in the cell. These include various stable RNAs, mRNAs, and aberrant transcripts both in the nucleus and in the cytoplasm.

In this work I characterize the three members of the exosome “cap”, the RNA binding proteins Rrp4, Rrp40, and Csl4. I determine that in spite of their structural similarity, they each have a unique essential role. Second, I determine that two of the cap proteins Rrp4 and Rrp40 have a role in bridging subunits of the PH ring of the exosome. The third cap protein Csl4 was shown not to have a bridging role. Further, I show that stable interaction with the exosome is not required for the essential role of Csl4.

In addition, I look at the physiological importance of the nuclease domains of the exosome. I show that the exonuclease is the primary activity for the exosome and that in its absence the iron starvation response of the cell is activated.

Despite numerous studies of the exosome, only a few address the physiological relevance of the catalytic activity. This work shows that the exonuclease of the exosome is important for oxidative stress protection and affects glucose metabolism and provides a basis for future research into the physiological importance of this essential RNase.

Research Info

Characterization of the RNA binding and RNA degrading subunits of the eukaryotic exosome