Pawel Grzechnik lab at the University of Birmingham

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We study how RNA synthesis controls gene expression in eukaryotic cells

Faculty of Biology, Medicine and Health

School of Biological Sciences

Michael Smith Building
Oxford Road
Manchester M13 9PT

Our research aims to understand mechanisms regulating RNA Polymerase II
and co-transcriptional RNA processing in normal and diseased eukaryotic cells

Oncoproteins in the regulation of the transcriptional cycle

how gene expression is controlled in healthy and cancer cells
regulation of transcription elongation
the molecular mechanisms driving carcinogenesis

The human protein CREPT (Cell cycle-Related and expression-Elevated Protein in Tumor) is a proto-oncogene interacting with the C-terminal domain (CTD) of RNA Polymerase II which has been shown to be overexpressed in 80% of cancers. Our goal is to understand the functions of CREPT and his interactors in the regulation of gene expression.

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
phosphorylation of Pol II CTD

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 protects RNA from 5'-3' degradation and is essential for mRNA export and translation. Our research aims to elucidate how the presence of the cap influences transcribing RNA Polymerase II and regulates the transcriptional cycle.

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

Onofrio Zanin

MIBTP PhD student

“Considerate la vostra semenza: fatti non foste a viver come bruti, ma per seguir virtute e canoscenza”

Ulisse, "Canto XXVI of the Inferno", Divina Commedia

MSc: University of Trieste

contact: OXZ813 (at) student.bham.ac.uk

Hurmuz Ceylan

PhD student

"I haven’t failed. I just found 10.000 ways that won’t work"

Thomas Edison

MSc: Gebze Technical University

contact: HXC896 (at) student.bham.ac.uk

Aytaj Nabiyeva

PhD student

"You will face a problem with every step you take. Don't waste your time crying, you won't have time to settle"

Yasin Nabiyev

BSc: Baku State University

MSc: Azerbaijan National Academy of Sciences

contact: (at) student.bham.ac.uk

Papers

Zanin O., Hebenstreit D., Grzechnik P. (2022) Ceg1 depletion reveals mechanisms governing degradation of non-capped RNAs. BioRxiv; doi:10.1101/2022.09.24.509330; [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

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]

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 how RNA synthesis controls gene expression in eukaryotic cells

Our research aims to understand mechanisms regulating RNA Polymerase II and co-transcriptional RNA processing in normal and diseased eukaryotic cells

Oncoproteins in the regulation of the transcriptional cycle

​

Molecular mechanisms of Prader-Willi Syndrome

​

Roles for mRNA capping in transcription

​

The Team

Dr Pawel Grzechnik

Principal Investigator

​

Dr Kinga Winczura

Postdoctoral Researcher

​

Onofrio Zanin

MIBTP PhD student

​

Hurmuz Ceylan

PhD student

​

Aytaj Nabiyeva

PhD student

Our research aims to understand mechanisms regulating RNA Polymerase II
and co-transcriptional RNA processing in normal and diseased eukaryotic cells