Description
- Abstract:
- A detailed understanding of ribosomal RNA (rRNA) structure is essential to understanding its function in the cell. Here we present a new comparative phylogenetic analysis of eukaryotic rRNA and define discrete nucleotide motifs that display a high sequence and structural conservation within the entire eukaryotic domain of life. We integrated aligning techniques with the rRNA structural analysis software ARB and the SILVA database containing 12,506 rRNA sequences. Our analysis of 23-28S rRNA identified 42 eukaryotic conserved nucleotide elements (eCNEs). Homology modeling revealed that eCNEs cluster in folded rRNA. To explore the function of eCNEs, we studied one (eCNE6) that is conserved in Eukarya but degenerate in Bacteria. eCNE6 contacts ribosomal protein Rpl32, which lacks a bacterial homologue. Depletion of RPL32 in yeast leads to rapid accumulation of 35S pre-rRNA. In response to this processing defect, cells rapidly arrest in G1 phase of the cell cycle and increase in cell volume. Unexpectedly, we detect a disproportional relationship between cell mass and volume due to degradation of mature ribosomal subunits. The accelerated degradation of ribosomes is dependent on the ubiquitin deconjugation enzyme Ubp3, an enzyme required for cargo specific ribosomal autophaghy (ribophagy). Indeed, we detect autophagic bodies in cells with impaired ribosome biogenesis. These results imply that attenuating ribosome biogenesis at an early step mimics a starvation state, inhibits cell cycle progression, and promotes autophagic destruction of the ribosomal subunits.
- Notes:
- Thesis (Ph.D.) -- Brown University (2010)
Access Conditions
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Citation
Doris, Stephen M.,
"Computational Phylogenetics Reveals Conserved Motifs in Ribosomal RNA that Link Ribosome Biogenesis with Cell Cycle and Autophagy in Eukaryotes"
(2009).
Biology and Medicine Theses and Dissertations, Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0BK19NN
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