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Laboratory of gene expression regulation

Principal investigator : Dr. Petr Folk, Dr. František Půta

Most eukaryotic protein-coding transcripts contain introns, which vary in number, length, and position along the transcript body. Splicing - the process of intron removal - is linked to RNA transcription and affected by the microenvironment formed by the surrounding chromatin, intrinsically disordered proteins and RNAs. Both Saccharomyces cerevisiae and Schizosaccharomyces pombe are excellent models to study spliceosome assembly, splicing and mRNA export. In recent years, spliceosome structures from various stages of the splicing cycle were resolved using electron tomography. This structural information can now be exploited using powerful molecular genetic tools available for the yeast models.

Research interest in brief

We study the mechanisms of splicing regulation and the relationship between splicing and transcription using yeast as model organisms. We analyzed, using gene targeting and site directed mutagenesis, the essential function of the splicing factor SNW/SKIP in unicellular eukaryotes. We proposed a model for SNW/SKIP function, in which the protein targets the enzymatic activity of peptidyl-prolyl cis-trans isomerase to the multiprotein complexes associated with RNA PolII during transcription initiation and splicing.

Our current interest focuses on the roles of RNA structures in the regulation of splicing. pre-mRNAs can form secondary and higher order structures, which have the potential to either enhance or block splicing signals. The formation of such structures and their stability is an important factor in the complex interplay of splicing factors, snRNAs, regulatory proteins and chromatin microenvironment.

Keywords: Cell signaling - Gene expression - Splicing – RNA structure

Selected references

Abrhámová K, Nemčko F, Libus J, Převorovský M, Hálová M, Půta F, Folk P. (2018) Introns provide a platform for intergenic regulatory feedback of RPL22 paralogs in yeast. PLoS One. 5;13(1):e0190685. doi: 10.1371/journal.pone.0190685. eCollection 2018.

Hálová M, Gahura O, Převorovský M, Cit Z, Novotný M, Valentová A, Abrhámová K, Půta F, Folk P. (2017). Nineteen complex-related factor Prp45 is required for the early stages of cotranscriptional spliceosome assembly. RNA 23(10):1512-1524. doi: 10.1261/rna.061986.117. Epub 2017 Jul 12.

Převorovský M, Oravcová M, Zach R, Jordáková A, Bähler J, Půta F, Folk P. (2016) CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast. Cell Cycle 15(22):3082-3093. Epub 2016 Sep 29.

Převorovský M, Oravcová M, Tvarůžková J, Zach R, Folk P, Půta F, Bähler J. (2015) Fission Yeast CSL Transcription Factors: Mapping Their Target Genes and Biological Roles. PLoS One. 10(9):e0137820. doi: 10.1371/journal.pone.0137820. eCollection 2015.

Gahura, O., Hamman, C., Valentova, A., Puta, F., and Folk. P. (2011) Secondary structure is required for 3′ splice site recognition in yeast. Nucleic Acid Res. 39(22): 9759-9767.

Contact information

Doc. RNDr. Petr Folk, CSc.  petr.folk@natur.cuni.cz
Doc. RNDr. František Půta, CSc.  frantisek.puta@natur.cuni.cz
Mgr. Kateřina Abrhámová, Ph.D.  katerina.abrhamova@natur.cuni.cz
RNDr. Jiří Libus, Ph.D. jiri.libus@natur.

Laboratory: Viničná 5, lower level, door n. S08; tel. 22195 1785

 

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