Povezanost signalnog puta NMD s alternativnim produljenjem telomera i preživljenjem stanica Saccharomyces cerevisiae

master's thesis

• Title (english): Investigating the link between nonsense-mediated mRNA decay pathway and survivor formation in Saccharomyces cerevisiae
• Author: Alan Kavšek
• Mentor: Michael Chang (mentor)
• Mentor: Vlatka Zoldoš (mentor)
• Committee member: Vlatka Zoldoš (predsjednik povjerenstva)
• Committee member: Damjan Franjević (član povjerenstva)
• Committee member: Jasna Hrenović (član povjerenstva)
• Committee member: Ivana Ivančić Baće (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2017-02-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Degradacija molekula mRNA s besmislenim mutacijama (NMD) kontrolni je mehanizam koji selektivno razgrađuje mRNA s preuranjenim završnim kodonom (PTC). Istraživanja pokazuju da NMD regulira i koncentraciju mnogih mRNA koje ne sadrže PTC te da je time uključen u kontrolu određenih staničnih procesa, konkretno nastanak preživjelih stanica tipa II. Ovo istraživanje ispituje ovisnost nastanka takvih stanica o ekspresiji gena UPF1, UPF2 i UPF3, koji čine NMD u S. cerevisiae te gena EBS1, koji literatura povezuje s NMD. Također se istražuje direktna veza između NMD i nastanka preživjelih stanica tipa II, a kao vjerojatni kandidati su odabrani proteini Stn1 i Rad51. Rezultati pokazuju kako nastanak preživjelih stanica tipa II nije onemogućen pojačanom ekspresijom gena STN1. Potrebno je ipak ispitati može li pojačana ekspresija gena STN1 djelomično ometati nastanak takvih stanica. U mutanata s pojačanom ekspresijom gena RAD51 nastanak preživjelih stanica spomenutog tipa nije primijećen. Ulogu tog gena kao veze između NMD i formiranja preživjelih stanica tipa II treba, međutim, dodatno ispitati jer je na rezultate mogao utjecati način provođenja eksperimenta. Opažanja opisana u radu podržavaju hipotezu da je NMD uključen u regulaciju nastanka preživjelih stanica tipa II, ali potrebna su dalja istraživanja kako bi se preciznije odredila priroda te veze.

Abstract (english)

Nonsense-mediated mRNA decay (NMD) is a eukaryotic mechanism of RNA surveillance that selectively degrades transcripts containing premature termination codons (PTC). Previous studies suggest that this pathway also regulates the abundance of many cellular mRNAs without a PTC. It is therefore very likely that it surveils certain cellular processes, among them regulation of type II survivor formation. This study tests whether the generation of type II survivors depends on the three genes composing NMD in S. cerevisiae – UPF1, UPF2 and UPF3. Dependency of this process on EBS1 is also examined because this gene is supposed to be connected to NMD. Furthermore, the exact connection between NMD and type II survivor formation is studied and two proteins, namely Stn1 and Rad51, are chosen as likely candidates for this link. In the case of STN1, results suggest that type II survivor generation is not blocked by overexpression of this gene. Whether it is partially impaired remains to be checked. Type II survivors have not been detected in mutants with RAD51 overexpression but the results may have been influenced by the way in which the assay was carried out. The observations made in this study enable a general conclusion that NMD is most likely involved in the regulation of type II survivors, while the exact link remains to be discovered.

• Keywords: Put degradacije molekula mRNA s besmislenim mutacijama (NMD); preživjele stanice tipa II; gen UPF1; gen UPF2; gen UPF3; gen STN1; gen RAD51
• Keywords (english): Nonsense-mediated mRNA decay (NMD); type II survivors; UPF1; UPF2; UPF3; STN1; RAD51
• Language: croatian
• URN:NBN: urn:nbn:hr:217:146329
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-20 12:37:18