Pawel Grzechnik lab at the University of Birmingham

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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

Research

Mechanisms controlling early stages of transcription in human cells

how gene expression is controlled in healthy and cancer cells
regulation of transcription elongation
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

processing of non-coding RNA
functions of ncRNA in neuronal development
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.

Roles for mRNA capping in transcription

cross-talk between nascent RNA and Pol II
hallmarks of mRNA synthesis
RNA stabilty

All transcripts generated by RNA Polymerase II are capped at their 5' ends by capping enzymes recruited to the CTD of Pol II. The cap plays a role in RNA stability and is essential for mRNA export and translation. Our research aims to elucidate how the presence of the cap affects RNA fate and the choice of the degradation pathway.

People

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

Martina Trantalovska

MSc student

"If we knew what we were doing, it would not be called research, would it?”

Albert Einstein

contact: martina.trantalovska(at)student.manchester.ac.uk

Papers

Papers

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]

Sledziowska M., Jones M., Almaghrabi R., 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]

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]

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]

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]

Winczura K.M., Grzechnik P. (2019) DNAzyme-dependent analysis of rRNA 2’-O-methylation. JoVE, 151, doi: 10.3791/59700. [PDF]

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]

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]

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]

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]

Grzechnik P., Gdula M. R., Proudfoot N.J. (2015) Pcf11 orchestrates transcription termination pathways in yeast. Genes Dev. 29, 849-61. [PDF]

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]

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]

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]

Grzechnik P., Kufel J. (2008) Polyadenylation linked to transcription termination directs the processing of snoRNA precursors in yeast. Mol. Cell 32, 247-58. [PDF]

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]

Phd positions available

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.

We study the mechanisms regulating RNA Polymerase II and co-transcriptional RNA processing in normal and diseased eukaryotic cells