1. Terminal RNA modifications in gene expression and viral infection
Supervisor: assoc.prof. Mgr. Štěpánka Vaňáčová, Ph.D.
Annotation:
Posttranscriptional RNA modifications possess key roles in diverse pathways in humans, including development, disease and infections. This PhD project will focus on the machines and role of terminal modifications of coding and noncoding RNAs. They can affect mRNA metabolism and protein synthesis by direct mRNA modifications or via tailing of regulatory noncoding RNAs (ncRNAs). The topic is a follow up of our studies of RNA processing and surveillance mechanisms in human cells mediated by terminal uridylyltransferases (TUTases) and terminal nucleotide transferases (TENTS). You will address the question of regulators of this pathway and its impact in viral infections.
The student will master diverse methodologies, such as human cell culture manipulations (cultivation, RNAi, CRISPR/Cas9, etc.), recombinant DNA preparation, protein expression and purification, high-throughput analyses and enzymatic assays.
She/he will have the opportunity to present the results at prestigious international conferences. Moreover, this project will involve collaboration with other leading researches in European institutes.
Recommended literature:
Zigáčková, D., Vaňáčová, Š. 2018 The role of 3′ end uridylation in RNA metabolism and cellular physiology. Phil. Trans. R. Soc. B 373 20180171; DOI: 10.1098/rstb.2018.0171.
Ustianenko, D; Pasulka J; Feketova, Z; Bednarik, L; Zigackova, D.; Fortova, A; Zavolan, M; Vanacova, S. 2016 TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured noncoding RNAs. EMBO Journal, 35:2179-2191. doi: 10.15252/embj.201694857
Hrossova, D., Sikorsky T., Potesil D., Bartosovic M., Pasulka J., Zdrahal Z., Stefl R., Vanacova S. 2015 RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3′-end extended forms of snRNAs. Nucleic Acids Res. 43:4236-48.
Ustianenko D., Hrossova D., Potesil D., Chalupnikova K., Hrazdilova K., Pachernik J., Cetkovska K., Uldrijan S., Zdrahal Z., Vanacova S. 2013 Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs. RNA 9:1632-8.
Keywords: RNA modifications, RNA processing, transcriptomics, proteomics, protein-RNA interactions
