A novel rRNA quality control function for Npl3 in Saccharomyces cerevisiae
von Anne-Sophie Lindemann
Datum der mündl. Prüfung:2024-03-13
Erschienen:2024-03-25
Betreuer:Prof. Dr. Heike Krebber
Gutachter:Prof. Dr. Heike Krebber
Gutachter:Prof. Dr. Ralf Ficner
Gutachter:Dr. Oliver Valerius
Gutachter:Prof. Dr. Jörg Stülke
Gutachter:Prof. Dr. Stefanie Pöggeler
Gutachter:PD Dr. Wilfried Kramer
Dateien
Name:240321 Thesis Lindemann.pdf
Size:4.02Mb
Format:PDF
Description:Thesis
Diese Datei ist bis 12.03.2025 gesperrt.
Zusammenfassung
Englisch
In all domains of life, ribosomes are essential complexes that are the sole source for protein synthesis. Ribosome biosynthesis, the most energy-consuming process in a cell, has to be tightly regulated. Misregulation of this process in mammals can lead to diseases like ribosomopathies, which are often associated with a predisposition for cancer. Furthermore, some cancer types exhibit an upregulation of certain ribosome biogenesis factors. The downregulation of these factors induces apoptosis in these cancer cells. Therefore, it is important to gain an in-depth knowledge of the ribosome biogenesis and its quality control, which is currently not well understood. This study demonstrates that the mRNA guard protein Npl3 is recruited co-transcriptionally to the pre-rRNA during early transcription. This RNA binding protein interacts with RNAPI and some SSU processome components in an RNA independent manner. Additionally, we show that Npl3 plays a crucial role in the accurate assembly of the SSU processome on the pre-rRNA, which in turn affects processing at cleavage sites A0, A1 and A2. Upon deletion of NPL3, an accumulation of aberrant 23S rRNA, and the 5’-A0 and A0-A1 fragments is observed. Our results indicate that this accumulation is a result of reduced binding of the TRAMP complex components Air1 and Air2, as well as the nuclear exosome component Rrp6 to the pre-rRNA in npl3Δ. Together, these results reveal a new function of Npl3 as a quality control factor for 18S rRNA maturation and that the function of the mRNA-guard protein is not restricted to messenger RNAs but extends its surveillance function to rRNA.
Keywords: SSU processome; Npl3; 23S rRNA; TRAMP; Air1