- Title Information
- Title
- Computational Phylogenetics Reveals Conserved Motifs in Ribosomal RNA that Link Ribosome Biogenesis with Cell Cycle and Autophagy in Eukaryotes
- Name:
Personal
- Name Part
- Doris, Stephen M.
- Role
- Role Term:
Text
- creator
- Origin Information
- Copyright Date
(keyDate="yes", encoding="w3cdtf")
- 2009
- Physical Description
- Extent
- x, 200 p.
- digitalOrigin
- born digital
- Note
- Thesis (Ph.D.) -- Brown University (2010)
- Name:
Personal
- Name Part
- Gerbi, Susan
- Role
- Role Term:
Text
- director
- Name:
Personal
- Name Part
- Dahlberg, Albert
- Role
- Role Term:
Text
- reader
- Name:
Personal
- Name Part
- Mowry, Kimberly
- Role
- Role Term:
Text
- reader
- Name:
Personal
- Name Part
- Serio, Tricia
- Role
- Role Term:
Text
- reader
- Name:
Personal
- Name Part
- Woolford, John
- Role
- Role Term:
Text
- reader
- Name:
Corporate
- Name Part
- Brown University. Division of Biology and Medicine. Molecular Biology, Cell Biology, and Biochemistry
- Role
- Role Term:
Text
- sponsor
- Genre (aat)
- theses
- 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.
- Subject (Local)
- Topic
- Phylogenetic analysis
- Subject (Local)
- Topic
- Ribosomal RNA
- Subject (Local)
- Topic
- Alignment
- Subject (Local)
- Topic
- Autophagy
- Subject (FAST)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/850178")
- Topic
- Cell cycle
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20091218
- Language
- Language Term:
Code (ISO639-2B)
- eng
- Language Term:
Text
- English
- Identifier:
DOI
- 10.7301/Z0BK19NN
- Access Condition:
rights statement
(href="http://rightsstatements.org/vocab/InC/1.0/")
- In Copyright
- Access Condition:
restriction on access
- Collection is open for research.
- Type of Resource (primo)
- dissertations