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dc.contributor.author
Leu, Philipp
dc.contributor.supervisor
Kutay, Ulrike
dc.contributor.supervisor
Hall, Michael
dc.contributor.supervisor
Weis, Karsten
dc.date.accessioned
2023-04-11T06:46:27Z
dc.date.available
2020-10-05T05:41:02Z
dc.date.available
2020-10-05T09:05:00Z
dc.date.available
2020-10-07T06:04:41Z
dc.date.available
2023-04-11T06:41:16Z
dc.date.available
2023-04-11T06:46:27Z
dc.date.issued
2020
dc.identifier.uri
http://hdl.handle.net/20.500.11850/444445
dc.identifier.doi
10.3929/ethz-b-000444445
dc.description.abstract
Ribosomes translate the information encoded on mRNAs into functional proteins, a key process found in all domains of life. The complex assembly of these macromolecular machines requires the coordinated interplay of a myriad of trans- acting factors, and takes place across several cellular compartments. Although the process of ribosome synthesis has been studied for decades, many mechanistic insights into ribosome assembly steps are still missing. Ribosome synthesis has high energetic costs and demands many cellular resources. Therefore, eukaryotes have developed multiple regulatory mechanisms by which they adjust the production of new ribosomes and maintain cellular homeostasis. For instance, several mechanisms have evolved in eukaryotes to allow the cell to transcriptionally regulate transcripts required for ribosome biogenesis. In this study, we characterize the transcription factor TBPL1, a close relative of the TATA-box binding protein TBP. TBPL1 has been demonstrated to be essential in the development of non-mammal metazoans and has been implicated in the transcriptional regulation of ribosomal protein genes in flies. Here, we demonstrate that human TBPL1 is a nuclear factor that binds to ribosomal protein genes besides various other genomic targets in somatic cells. We show that human TBPL1 co-purifies with the TFIIA components GTF2A1 and GTF2A2, which are required to nucleate a transcriptionally competent pre-initiation complex at target genes. We provide evidence of human TBPL1 binding to DNA, in particular to the ribosomal protein core promoters RPS9 and RPL4. Furthermore, we offer evidence that TBPL1 is mainly an activating transcription factor and show that the loss of TBPL1 downregulates various mRNA processing factors, components of the splicing machinery, and ribosome biogenesis factors. Most notably, we show that the interaction of TBPL1 with TFIIA is essential for productive 40S maturation, indicating a dependency of ribosome biogenesis on transcripts produced by TBPL1. In addition, a highly conserved phenylalanine residue of TBPL1 assists in DNA binding of TBPL1, which is functionally linked to productive 40S subunit synthesis. Finally, we suggest that the TBPL1 transcription system is used for the expression of many genes implicated in diverse cellular processes.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.title
The role of transcription factor TBPL1 in gene expression and biogenesis of 40S ribosomal subunits
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2020-10-05
ethz.size
226 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
en_US
ethz.identifier.diss
26811
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02517 - Institut für Biochemie / Institute of Biochemistry (IBC)::03543 - Kutay, Ulrike / Kutay, Ulrike
en_US
ethz.date.deposited
2020-10-05T05:42:09Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Closed access
en_US
ethz.rosetta.installDate
2020-10-05T09:05:12Z
ethz.rosetta.lastUpdated
2024-02-02T21:33:04Z
ethz.rosetta.versionExported
true
ethz.COinS
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