The roles of GTPases in biogenesis of the large ribosomal subunit

Thomé, Chairini Cássia

dc.contributor.advisor	Bohnsack, Katherine E Dr.
dc.contributor.author	Thomé, Chairini Cássia
dc.date.accessioned	2025-09-22T17:15:34Z
dc.date.issued	2025-09-22
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/16243
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-11520
dc.format.extent	163	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject.ddc	570	de
dc.title	The roles of GTPases in biogenesis of the large ribosomal subunit	de
dc.type	doctoralThesis	de
dc.contributor.referee	Bohnsack, Katherine E Dr.
dc.date.examination	2025-02-18	de
dc.description.abstracteng	Ribosomes are ribonucleoprotein complexes responsible for protein synthesis, and their biogenesis is a complex, highly orchestrated process requiring a significant amount of energy and the coordinated action of all three RNA polymerases. Disruptions in ribosomal subunit assembly can lead to dysfunctional ribosomes, causing severe congenital diseases (ribosomopathies), and may also contribute to tumorigenesis. Formation of the ribosomal subunits is coordinated by trans-acting ribosome biogenesis factors (RBFs) that mediate ribosomal RNA (rRNA) modification, folding and processing, as well as the incorporation and positioning of ribosomal proteins (RPs). GTPases are among the RBFs that consume energy to drive structural rearrangements of pre-ribosomal particles, and several of these enzymes play important roles in assembly of the large subunit. Much knowledge on ribosome biogenesis comes from the yeast Saccharomyces cerevisiae, and despite the conservation of key aspects of the process across eukaryotes, many human RBFs, including GTPases, remain to be fully characterised. Recent structural studies of human pre-60S particles have identified GTPBP4, GNL3, and GNL2 on the particles, suggest roles for these GTPases in 60S assembly, but their precise functions have remained elusive. Furthermore, another putative GTPase, GNL3L is enriched in nucleoli, a major site of ribosome assembly, but potential contributions of this enzyme to subunit assembly have remained unclear. This study focused on analysing the roles of GTPBP4, GNL2, GNL3 and GNL3L during large ribosomal subunit maturation. Proteomics analyses provide insights into the timing of recruitment of these proteins to pre-ribosomal particles and their subsequent release, as well as the influence of nucleotides on their pre-ribosome association. Analyses of pre-rRNA processing in cells expressing GTP binding and hydrolysis mutants allowed to differentiate between the requirement for the presence of these proteins and the importance of their nucleotide binding/catalytic activities. Protein-RNA crosslinking approaches were used to identify GNL3L binding sites on pre-ribosomes and map RNA contact sites on the GTPase. Expression of truncated versions of GNL3 and GNL3L allowed the contribution of individual domains to pre-ribosome association to be determined. Also, the importance of the GTPase activity of GNL3L for ribosome function was explored. Collectively, these data provide new insights into the functions of GTPBP4, GNL3, and GNL2 during assembly of the large ribosomal subunit in humans and support the involvement of an additional GTPase, GNL3L. These findings contribute to further understand the biogenesis of human cytosolic ribosomes and the roles of GTPases in this process.	de
dc.contributor.coReferee	Ficner, Ralf Prof. Dr.
dc.contributor.thirdReferee	Stülke, Jörg Prof. Dr.
dc.contributor.thirdReferee	Richter-Dennerlein, Ricarda Dr.
dc.contributor.thirdReferee	Dobbelstein, Matthias Prof. Dr.
dc.contributor.thirdReferee	Urlaub, Henning Prof. Dr.
dc.subject.eng	Ribosome biogenesis	de
dc.subject.eng	GTPase	de
dc.subject.eng	GTPBP4	de
dc.subject.eng	GNL2	de
dc.subject.eng	GNL3	de
dc.subject.eng	GNL3L	de
dc.subject.eng	ribosomal protein	de
dc.subject.eng	pre-rRNA processing	de
dc.subject.eng	ribosome biogenesis factors	de
dc.subject.eng	translation	de
dc.subject.eng	ribosomal RNA	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-16243-7
dc.date.embargoed	2026-02-17
dc.affiliation.institute	Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2026-02-17	de
dc.identifier.ppn	1936617609
dc.identifier.orcid	0009-0006-6703-7205	de
dc.notes.confirmationsent	Confirmation sent 2025-09-22T19:45:01	de

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