Naslov
The RNA exosome complex influences the cellular response to the anti-cancer drug 5-fluorouracil in yeast

Autori
Novačić, Ana ; Oskomić, Marina ; Žunar, Bojan ; Primig, Michael ; Stuparević, Igor

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22: From Science to Knowledge / Dulić, Morana ; Sinčić, Nino ; Vrhovac Madunić, Ivana - Zagreb, 2022, 44-44

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology: From Science to Knowledge (HDBMB22)

Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
5-fluorouracil, RNA exosome, yeast

Sažetak
5-fluorouracil (5-FU) is a widely used drug for the treatment of colon and breast cancer. It is an anti-metabolite that is incorporated into DNA and RNA molecules and interferes with various cellular processes. Cancer cells can become resistant to 5-FU, which can be a major obstacle to 5-FU-based therapies, especially since the molecular mechanisms underlying such resistance remain poorly understood. The RNA-based toxicity of 5-FU is thought to be related to the RNA exosome, a highly conserved exoribonuclease complex that degrades and processes practically all classes of RNAs in eukaryotic cells. Previous studies have shown that the depletion of Rrp6/EXOSC10 catalytic subunit of the RNA exosome results in pronounced sensitivity to 5-FU in yeast Saccharomyces cerevisiae and human cells. In this work, we sought to gain more insight into the involvement of different RNA exosome subunits and cofactors in the cellular response to 5-FU in yeast. We demonstrated that the Dis3 catalytic subunit, as well as certain nuclear-specific RNA exosome cofactors, are required to achieve physiological level of growth upon 5-FU treatment. Surprisingly, inactivation of certain RNA exosome cofactors increased the resistance of cells to treatment with 5-FU compared with wild-type cells, suggesting possible compensatory mechanisms that might confer resistance to such mutant cells. Given the high degree of conservation of the RNA exosome complex and its cofactors from yeast to human, these results contribute to elucidation of the molecular mechanisms of 5-FU resistance which may be of general importance.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija

POVEZANOST RADA