Povezanost razine ekspresije egzoribonukleaze Rrp6 sa staničnim odgovorom na antitumorski lijek 5-fluorouracil

master's thesis

• Title (english): The association between exoribonuclease Rrp6 expression level and the cellular response to the anti-cancer drug 5-fluorouracil
• Author: Marina Oskomić
• Mentor: Igor Stuparević (mentor)
• Committee member: Bojan Žunar (predsjednik povjerenstva)
• Committee member: Marta Popović (član povjerenstva)
• Committee member: Renata Teparić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2022-09-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Egzoribonukleaza Rrp6 je katalitička podjedinica RNA egzosoma, kompleksa koji sudjeluje u kontroli kvalitete RNA molekula u svim eukariotskim stanicama. U ovom radu je praćen odgovor stanica dva evolucijski udaljena kvasca, Saccharomyces cerevisiae i Schizosaccharomyces pombe, na tretman anti-tumorskim lijekom 5-fluorouracilom (5-FU), koji ometa stanične procese vezane uz RNA i DNA. Rezultati rada pokazuju kako tretman 5-FU utječe na razinu proteina Rrp6 pri fiziološkoj i povišenoj temperaturi te kako se promjena razine proteina Rrp6 u stanicama kvasca, postignuta delecijom ili prekomjernom ekspresijom odgovarajućeg gena, odražava na osjetljivost stanica na tretman s 5-FU. Osim Rrp6, u ovom radu pokazana je uključenost druge katalitičke podjedinice, Dis3 i kofaktora RNA egzosoma (Rrp47 i proteina TRAMP kompleksa) u otpornosti stanica na tretman s 5-FU. Zbog visoke evolucijske očuvanosti RNA egzosoma, dobiveni rezultati imaju implikacije za stanice viših eukariota te daju doprinos razjašnjavanju mehanizama otpornosti tumorskih stanica na tretman s 5-FU.

Abstract (english)

Rrp6 is the exoribonuclease catalytic subunit of the RNA exosome, a complex which participates in quality control of RNA molecules in all eukaryotic cells. This work monitored the cellular response of two evolutionarily distant yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, to treatment with the anti-cancer drug 5-fluorouracil (5-FU), which interferes with RNA- and DNA-related processes. The results show that 5-FU treatment affects the Rrp6 protein level at physiological and elevated temperatures. The change of Rrp6 level in yeast cells, achieved by gene deletion or overexpression of the corresponding gene, influences cellular sensitivity to 5-FU treatment. In addition to Rrp6, the involvement of the second RNA exosome catalytic subunit, Dis3 and its cofactors (Rrp47 and TRAMP complex) in resistance to 5-FU was also demonstrated. Due to the high evolutionary conservation of the RNA exosome complex, these results have implications for higher eukaryotes and contribute to clarifying the mechanisms of cancer cell resistance to 5-FU.

• Keywords: Rrp6; RNA egzosom; 5-FU; Saccharomyces cerevisiae; Schizosaccharomyces pombe
• Keywords (english): Rrp6; RNA exosome; 5-FU; Saccharomyces cerevisiae; Schizosaccharomyces pombe
• Language: croatian
• URN:NBN: urn:nbn:hr:159:119309
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-04-05 10:47:21