CeNT
herb

Interdisciplinary Laboratory of Molecular Biology and Biophysics

The Laboratory’s main field of interest focuses on the so-called cap structures, i.e. the modified nucleotides that decorate the 5’ ends of eukaryotic mRNAs and many snRNAs. Our current activities cover interdisciplinary studies on the molecular mechanisms of interactions between cap structures and protein regulator factors that are involved in processes of protein biosynthesis, RNA degradation and RNA recognition by cellular sensors. Results of our work will allow us to understand the significance of cap structure modifications in coordination of various functional processes that take place throughout the mRNA life cycle.

Furthermore, attempts are made to combine basic research with practical applications in order to design and synthesize mRNA transcripts that are stable and highly active translationally in a cell, which in turn can be used for biotechnological protein production and development of mRNA-based therapies. Our long-term goal is to develop modern mRNA-based drugs for protein replacement therapies or stem cells reprogramming. In our research we use a broad range of chemical, biological and biophysical methodologies. Our team cooperates with several laboratories located both in Poland and abroad.

Prof. Edward Darżynkiewicz
email: e.darzynkiewicz@cent.uw.edu.pl
room: 02.224


Stapled anoplin as an antibacterial agent
Monika Wojciechowska, Julia Macyszyn, Joanna Miszkiewicz, Renata Grzela, Joanna Trylska
Front. Microbiol., 13 December 2021
Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation.
Alison Galloway, Aneesa Kaskar, Dimitrinka Ditsova, Abdelmadjid Atrih, Harunori Yoshikawa, Carolina Gomez-Moreira, Olga Suska, Marcin Warmiński, Renata Grzela, Angus I Lamond, Edward Darżynkiewicz, Jacek Jemielity, Victoria H Cowling
Nucleic Acids Research, 49(12): 6722–6738.
Insight into the Binding and Hydrolytic Preferences of hNudt16 Based on Nucleotide Diphosphate Substrates.
Magdalena Chrabąszczewska, Maria Winiewska-Szajewska, Natalia Ostrowska, Elżbieta Bojarska, Janusz Stępiński, Łukasz Mancewicz, Maciej Łukaszewicz, Joanna Trylska, Michał Taube, Maciej Kozak, Edward Darżynkiewicz, Renata Grzela
International Journal of Molecular Sciences, 22(20):10929
Kinetic analysis of IFIT1 and IFIT5 interactions with different native and engineered RNAs and its consequences for designing mRNA-based therapeutics
Miedziak, B., Dobieżyńska, A., Darżynkiewicz, Z. M., Bartkowska, J., Miszkiewicz, J., Kowalska, J., ... & Darzynkiewicz, E.
RNA, 26(1), 58-68.
Development of bis-ANS-based modified fluorescence titration assay for IFIT/RNA studies
Dobieżyńska, A., Miszkiewicz, J., Darżynkiewicz, Z. M., Tyras, M., Stankiewicz-Drogoń, A., Trylska, J., ... & Grzela, R.
Biochemical and Biophysical Research Communications, 533(3), 391-396
CAP-MAP: cap analysis protocol with minimal analyte processing, a rapid and sensitive approach to analysing mRNA cap structures
Galloway A, Atrih A, Grzela R, Darzynkiewicz E, Ferguson MAJ, Cowling VH.
Open Biology. 2020
Effect of the His-Tag Location on Decapping Scavenger Enzymes and Their Hydrolytic Activity toward Cap Analogs
Ferenc-Mrozek, A., Bojarska, E., Stepinski, J., Darzynkiewicz, E., & Lukaszewicz, M.
ACS omega, 5(19)
Decapping Scavenger Enzyme Activity toward N2-Substituted 5′ End mRNA Cap Analogues
Pietrow, P., Ferenc-Mrozek, A., Piecyk, K., Bojarska, E., Darzynkiewicz, E., & Jankowska-Anyszka, M.
ACS omega, 4(17), 17576-17580.
Modified ARCA analogs providing enhanced translational properties of capped mRNAs
Kocmik, I., Piecyk, K., Rudzinska, M., Niedzwiecka, A., Darzynkiewicz, E., Grzela, R., & Jankowska-Anyszka, M. (2018).
Cell Cycle
Hydrolytic activity of human Nudt16 enzyme towards dinucleotide cap analogs and short capped oligonucleotides
Grzela, R., Nasilowska, K., Lukaszewicz, M., Tyras, M., Stepinski, J., Jankowska-Anyszka, M., ... & Darzynkiewicz, E.(2018).
RNA, rna-065698
Amino-Functionalized 5′ Cap Analogs as Tools for Site-Specific Sequence-Independent Labeling of mRNA
Warminski, M., Sikorski, P. J., Warminska, Z., Lukaszewicz, M., Kropiwnicka, A., Zuberek, J., Darzynkiewicz, E., Kowalska, J. Darzynkiewicz, E., Kowalska, J. & Jemielity, J. (2017).
ioconjugate chemistry, 28(7), pp.1978-1992.
Quantum dots use both LUMO and surface trap electrons in photoreduction proces, Journal of Luminescence
Darżynkiewicz, Z. M., Pędziwiatr, M., & Grzyb, J. (2017).
Journal of Luminescence, 183, 401-409.
Molecular recognition of mRNA 5′ cap by 3′ poly(A)-specific ribonuclease (PARN) differs from interactions known for other cap-binding proteins
Niedzwiecka, A., Nilsson, P., Worch, R., Stepinski, J., Darzynkiewicz, E., & Virtanen, A. (2016)
Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1864(4), 331-345
Phosphate-modified analogues of m7GTP and m7Gppppm7G – synthesis and biochemical properties
Ziemniak, M., Kowalska, J., Lukaszewicz, M., Zuberek, J., Wnek, K., Darzynkiewicz, E., & Jemielity, J. (2015)
Bioorganic & medicinal chemistry, 23(17), 5369-5381
How to find the optimal partner-studies of snurportin 1 interactions with U snRNA 5’ TMG-cap analogues containing modified 2-amino group of 7-methylguanosine
Piecyk, K., Niedzwiecka, A., Ferenc-Mrozek, A., Lukaszewicz, M., Darzynkiewicz, E., & Jankowska-Anyszka, M. (2015)
Bioorganic & medicinal chemistry, 23(15), 4660-4668
Effect of different N7 substitution of dimucleotide cap analogs on the hydrolytic susceptibility towards scavenger decapping enzymes (DcpS)
Piecyk, K., Darzynkiewicz, Z. M., Jankowska-Anyszka, M., Ferenc-Mrozek, A., Stepinski, J., Darzynkiewicz, E., & Bojarska, E. (2015)
Biochemical and biophysical research communications, 464(1), 89-93
District Features of Cap Binding by eIF4E1b Proteins
Kubacka, D., Miguel, R. N., Minshall, N., Darzynkiewicz, E., Standart, N., & Zuberek, J.
Journal of molecular biology, 427(2), 387-405.
Five eIF4E isoforms from Arabidopsis thaliana are characterized by distinct features of cap analogs binding.
Kropiwnicka, A., Kuchta, K., Lukaszewicz, M., Kowalska, J., Jemielity, J., Ginalski, K., ... & Zuberek, J. (2015).
Biochemical and biophysical research communications, 456(1), 47-52.
Distinct Features of Cap Binding by eIF4E1b Proteins
Kubacka, D., Miguel, R. N., Minshall, N., Darzynkiewicz, E., Standart, N., & Zuberek, J. (2015)
Journal of molecular biology, 427(2), 387-405
mRNA and snRNA Cap Analogs: Synthesis and Applications.
Stepinski, J., & Darzynkiewicz, E. (2014).
Chemical Biology of Nucleic Acids (pp. 511-561). Springer, Berlin, Heidelberg.
eIF4F-like complexes formed by cap-binding homolog TbEIF4E5 with TbEIF4G1 or TbEIF4G2 are implicated in post-transcriptional regulation in Trypanosoma brucei.
Freire, E. R., Vashisht, A. A., Malvezzi, A. M., Zuberek, J., Langousis, G., Saada, E. A., ... & Neto, O. P. D. M. (2014).
RNA, 20(8), 1272-1286.
Triazole-containing monophosphate mRNA cap analogs as effective translation inhibitors.
Piecyk, K., Lukaszewicz, M., Darzynkiewicz, E., & Jankowska-Anyszka, M. (2014).
RNA, 20(10), 1539-1547.
Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.
Freire, E. R., Malvezzi, A. M., Vashisht, A. A., Zuberek, J., Saada, E. A., Langousis, G., ... & de Melo Neto, O. P. (2014).
Eukaryotic cell, 13(7), 896-908.
Towards novel efficient and stable nuclear import signals: synthesis and properties of trimethylguanosine cap analogs modified within the 5′, 5′-triphosphate bridge.
Zytek, M., Kowalska, J., Lukaszewicz, M., Wojtczak, B. A., Zuberek, J., Ferenc-Mrozek, A., ... & Jemielity, J. (2014).
Organic & biomolecular chemistry, 12(45), 9184-9199.
Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.
Kowalska, J., Wypijewska del Nogal, A., Darzynkiewicz, Z. M., Buck, J., Nicola, C., Kuhn, A. N., ... & Maciejczyk, M. (2014).
Nucleic acids research, 42(16), 10245-10264.
Structural analysis of human 2′-O-ribose methyltransferases involved in mRNA cap structure formation.
Smietanski, M., Werner, M., Purta, E., Kaminska, K. H., Stepinski, J., Darzynkiewicz, E., ... & Bujnicki, J. M. (2014).
Nature communications, 5, 3004.
Synthesis, properities and biological activity of boranophosphate analogs of the mRNA cap: versalite tools for manipulation of therapeutically relevant cap-dependent processes
Kowalska, J., Wypijewska del Nogal, A., Darzynkiewicz, Z. M., Buck, J., Nicola, C., Kuhn, A. N., ... & Maciejczyk, M. (2014)
Nucleic acids research, 42(16), 10245-10264
Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.
Kowalska, J., Wypijewska del Nogal, A., Darzynkiewicz, Z. M., Buck, J., Nicola, C., Kuhn, A. N., ... & Maciejczyk, M. (2014).
Nucleic acids research, 42(16), 10245-10264.
Synthesis, properties, and biological activity of boranophosphate analogs of the mRNA cap: versatile tools for manipulation of therapeutically relevant cap-dependent processes.
Kowalska, J., Wypijewska del Nogal, A., Darzynkiewicz, Z. M., Buck, J., Nicola, C., Kuhn, A. N., ... & Maciejczyk, M. (2014).
Nucleic acids research, 42(16), 10245-10264.
Trypanosoma brucei translation initiation factor homolog EIF4E6 forms a tripartite cytosolic complex with EIF4G5 and a capping enzyme homolog.
Freire, E. R., Malvezzi, A. M., Vashisht, A. A., Zuberek, J., Saada, E. A., Langousis, G., ... & de Melo Neto, O. P. (2014).
Eukaryotic cell, 13(7), 896-908.
Synthesis and evaluation of stability of m 3 G-CAP analogues in serum-supplemented medium and cytosolic extract.
Honcharenko, M., Zytek, M., Bestas, B., Moreno, P., Jemielity, J., Darzynkiewicz, E., ... & Strömberg, R. (2013).
Bioorganic & medicinal chemistry, 21(24), 7921-7928.
Synthesis and evaluation of fluorescent cap analogues for mRNA labelling.
Ziemniak, M., Szabelski, M., Lukaszewicz, M., Nowicka, A., Darzynkiewicz, E., Rhoads, R. E., ... & Jemielity, J. (2013).
RSC advances, 3(43), 20943-20958.