Faculty of Biology, Medicine and Health
School of Biological Sciences
Division of Molecular and Cellular Function
We study the mechanisms regulating RNA Polymerase II
and co-transcriptional RNA processing in normal and diseased eukaryotic cells
Mechanisms controlling early stages of transcription in human cells
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how gene expression is controlled in healthy and cancer cells
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regulation of transcription elongation
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the molecular mechanisms driving carcinogenesis
Human RPRD (Regulation of nuclear pre-mRNA domain-containing protein) proteins RPRD1A, RPRD1B and RPRD2 are novel proteins directly interacting with RNA Polymerase II and their deregulation is associated with carcinogenesis. Our goal is to understand the functions of RPRDs in transcription and regulation of gene expression as well as to investigate their link with cancer.
Molecular mechanisms of Prader-Willi Syndrome
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processing of non-coding RNA
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functions of ncRNA in neuronal development
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regulation of gene expression in PWS
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder recognized as the most common genetic cause of life-threatening obesity. In our project, we study the impact of PWS-related ncRNAs on gene expression in induced pluripotent stem cells (iPSC). Our approach will allow to understand how ncRNA regulate neuronal development.
Antisense oligonucleotides (ASOs) targeting nascent RNA
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new targets for ASOs
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nascent transcription
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genetic diseases
Antisense oligonucleotides (ASOs) are short, synthetic nucleic acids that bind to complementary RNA sequences and alter gene expression, making them versatile therapeutic agents. We are investigating how ASOs target the nascent transcriptome, offering new therapeutic opportunities.
The Team
Dr Pawel Grzechnik
Principal Investigator
"If it bleeds, we can kill it"
Dutch, "Predator"
MSc: University of Warsaw
PhD: University of Warsaw
Postdoc: University of Oxford
contact: pawel.grzechnik(at)manchester.ac.uk
Dr Kinga Winczura
Postdoctoral Researcher
"So much science, so little time"
Nick Proudfoot
MSc: University of Warsaw
PhD: Aarhus University
contact: kinga.winczura(at)manchester.ac.uk
Huriye Ilhan
PhD student
"Science is the only true guide in life"
Mustafa Kemal Atatürk
MSc: Konya Food and Agriculture University
contact: huriye.ilhan(at)postgrad.manchester.ac.uk
Karishma Panchani
MSc student
TBC
TBC
contact: TBC
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Papers
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Winczura K., Joenson L., Koller E., Grzechnik P.*, Kielpinski L.J.K.* (2026) Antisense oligonucleotides targeting transcription termination windows disrupt mRNA 3' end processing and decrease gene expression. BioRxiv; doi:10.64898/2026.02.04.703595; [PDF] *joint communication author
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Grzechnik P., Mischo H. (2025) Fateful decisions of where to cut the line: Pathology associated with aberrant 3' end processing and transcription termination. J. Mol. Biol. doi: 10.1016/j.jmb.2024.168802 [PDF]
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Zanin O., Eastham E., Winczura K., Ashe M., Martinez-Nunez R.T., Hebenstreit D., Grzechnik P. (2023) Ceg1 depletion reveals mechanisms governing degradation of non-capped RNAs. Commun. Biol. 6 (112); doi:10.1038/s42003-023-05495-6 [PDF]
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Sledziowska M., Winczura K., Jones M., Almaghrabi R., Mischo H., Hebenstreit D., Garcia P., Grzechnik P. (2022) Non-coding RNAs associated with Prader-Willi syndrome regulate transcription of neuronal genes in human induced pluripotent stem cells. Hum. Mol. Gen. doi:20.1093/hmg/ddac228 [PDF]
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Winczura K., Ceylan H., Sledziowska M., Jones M., Fagarasan H., Wang J., Saponaro M., Arnold R., Hebenstreit D., Grzechnik P. (2021) RPRD proteins regulate transcription in human cells. BioRxiv; doi:10.1101/2021.06.20.449126; [PDF]
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Heo D.H, Kus K., Grzechnik P., Tan-Wong S.M., Birot A., Kecman T., Nielsen S., Zenkin N., Vasiljeva L. (2021) Transcription and chromatin-based surveillance mechanism controls suppression of cryptic antisense transcription. Cell Rep. 36, doi:10.1016/j.celrep.2021.109671 [PDF]
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Melidis L., Hill H.J., Coltman N.J., Davies S.P., Winczura K., Chauchan T., Craig J.S., Garai A., Hooper C.J., Edgan R.T., McKeating J.A., Hodges N.J., Stamataki Z.*, Grzechnik P.*, Hannon M.J.* (2021). Supramolecular cylinders target bulge structures in the 5’ UTR of the RNA genome of SARS-Cov-2 and inhibit viral replication. Angew. Chem. doi:10.1002/anie.202104179; BioRxiv doi:10.1101/2021.03.30.437757; *joint communication author [PDF]
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Winczura K.M., Grzechnik P. (2019) DNAzyme-dependent analysis of rRNA 2’-O-methylation. JoVE, 151, doi: 10.3791/59700. [PDF]
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Kufel J., Grzechnik P. (2019) snoRNAs tell a different tale. Trends Genet., 35, 104-117, doi: 10.1016/j.tig.2018.11.005 Review. [PDF]
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Pettinati I., Grzechnik P., Ribeiro de Almeida C., Brem J., McDonough M.A., Dhir S., Gannon J., Proudfoot N.J., Schofield C.J. (2018) Biosynthesis of histone messenger RNA employs a specific 3’ endonuclease. eLife, 7 pii:398865, doi: 10.7554/eLife.39865 [PDF]
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Lidschreiber M., Easter A.D., Battaglia S., Rodríguez-Molina R.B., Casañal A., Carminati M., Baejen C., Grzechnik P., Maier K.C., Cramer P., Passmore L.A. (2018) The APT complex is involved in non-coding RNA transcription and is distinct from CPF. Nucleic Acids Res. 46,11528-38 [PDF]
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Grzechnik P.*, Szczepaniak A.S., Dhir S., Pastucha A., Parslow H., Matuszek Z., Mischo H., Kufel J., Proudfoot N.J. (2018) Nuclear fate of yeast snoRNA is determined by co-transcriptional Rnt1 cleavage. Nat. Commun., 9:1783. *joint communication author [PDF]
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Grzechnik P., Gdula M. R., Proudfoot N.J. (2015) Pcf11 orchestrates transcription termination pathways in yeast. Genes Dev. 29, 849-61. [PDF]
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Grzechnik P., Tan-Wong S.M., Proudfoot N.J. (2014) Terminate and make a loop: regulation of transcriptional directionality. Trends Biochem. Sci. 39, 319-327. Review. [PDF]
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Skowronek E., Grzechnik P., Späth B., Marchfelder A., Kufel J. (2014) tRNA 3' processing in yeast involves tRNase Z, Rex1, and Rrp6. RNA 20, 115-30. [PDF]
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Mischo H.E., Gómez-González B., Grzechnik P., Rondón A.G., Wei W., Steinmetz L., Aguilera A., Proudfoot N.J. (2011) Yeast Sen1 helicase protects the genome from transcription-associated instability. Mol. Cell 41, 21-32. [PDF]
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Grzechnik P., Kufel J. (2008) Polyadenylation linked to transcription termination directs the processing of snoRNA precursors in yeast. Mol. Cell 32, 247-58. [PDF]
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Piwowarski J., Grzechnik P., Dziembowski A., Dmochowska A., Minczuk M., Stepien P. P. (2003) Human polynucleotide phosphorylase, hPNPase, is localized in mitochondria. J. Mol. Biol. 329, 853-7. [PDF]
Join us
If you are interested in RNA biology and would like to join the lab as an undergraduate student, a PhD student or a postdoc,
contact Pawel directly:
pawel.grzechnik (at) manchester.ac.uk
If you wish to apply for your own funding we will help you to develop your project and application.