The role of long non-coding RNAs and the RNA exosome in regulation of gene expression

doctoral thesis

• Title (croatian): Uloga dugih nekodirajućih molekula RNA i RNA egzosoma u regulaciji ekspresije gena
• Author: Novačić Ana
• Mentor: Igor Stuparević (mentor)
• Committee member: Ivan Krešimir Svetec (predsjednik povjerenstva)
• Committee member: Renata Teparić (član povjerenstva)
• Committee member: Marta Popović (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: 2023-12-07, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology
• Universal decimal classification (UDC): 578/579 - Virology. Microbiology

Abstract

The RNA exosome is a conserved protein complex involved in 3'-to-5' degradation and processing of all types of RNA classes in eukaryotic cells. The recently characterized substrates of the RNA exosome complex are long non-coding RNAs (lncRNAs), transcripts that do not code for proteins, but have the potential to regulate gene expression. The main objective of this work was to determine the role of lncRNAs and the RNA exosome complex in the regulation of stress-related genes in yeast. This work demonstrates that the RNA exosome is critical for maintaining yeast cell wall stability by regulating the expression of genes encoding enzymes involved in protein glycosylation, which is essential for supporting the cell wall structure. In maintaining cell wall stability, the RNA exosome functions in parallel with Ssd1, an RNA-binding protein that regulates translation of cell wall-related mRNAs. Furthermore, this work elucidates the molecular mechanisms through which lncRNAs and the RNA exosome regulate the expression of stress-related genes. A regulatory role has been demonstrated for the lncRNA transcribed at the gene locus encoding the protein Psa1, which is involved in the synthesis of the mannosylation precursor. Furthermore, this work demonstrates a negative regulatory role of antisense transcription at the PHO5 model gene locus at the level of promoter chromatin structure.

Abstract (croatian)

RNA egzosom je evolucijski očuvani proteinski kompleks uključen u razgradnju i procesiranje svih klasa RNA u smjeru 3'-5' u eukariotskim stanicama. Nedavno karakterizirani supstrati RNA egzosoma su duge nekodirajuće molekule RNA (lncRNA), transkripti koji ne nose uputu za sintezu proteina, ali imaju potencijalne uloge u regulaciji ekspresije gena. Glavni cilj ovog rada bio je odrediti ulogu lncRNA i kompleksa RNA egzosoma u regulaciji ekspresije gena kvasca čija je funkcija povezana sa stresom. Ovaj rad pokazuje da je RNA egzosom ključan za održavanje stabilnosti stanične stijenke kvasca, budući da regulira ekspresiju gena koji kodiraju za enzime uključene u glikozilaciju proteina, koja je bitna za održavanje strukture stanične stijenke. U održavanju stabilnosti stanične stijenke, RNA egzosom funkcionira paralelno sa Ssd1, RNA-vezujućim proteinom koji regulira translaciju mRNA koje nose upute za proteine uključene u staničnu morfogenezu. Nadalje, ovaj rad razjašnjava molekularne mehanizme putem kojih lncRNA i RNA egzosom reguliraju ekspresiju gena povezanih sa stresom. Pokazana je regulatorna uloga lncRNA transkribirane na lokusu gena koji kodira za protein Psa1, koji je uključen u sintezu manozilacijskog prekursora. Dodatno, ovim je radom pokazana negativna regulatorna ulogu antisense transkripcije na lokusu modelnog gena PHO5 na razini strukture kromatina promotorske regije.

• Keywords: gene expression; lncRNAs; RNA exosome; stress conditions; yeast S. cerevisiae
• Keywords (english): ekspresija gena; lncRNA; RNA egzosom; stresni uvjeti; kvasac S. cerevisiae
• Language: english
• URN:NBN: urn:nbn:hr:159:982678
• Promotion: 2023
• Study programme: Title: Postgraduate PhD Study in Nutrition; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biotehničkih znanosti, polje nutricionizam (doktor/doktorica znanosti, područje biotehničkih znanosti, polje nutricionizam)
• Type of resource: Text
• Extent: 106 str. : 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-23 11:11:24