Beyer, Andreas | Hänsel-Hertsch, Robert - C 02
Detecting transcriptional mistakes of RNA Polymerase-II at the single-cell level
Prof. Dr. Andreas Beyer
Institute for Genetics | CECAD Research Center
CMMC - PI - C 02
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Institute for Genetics | CECAD Research Center
Joseph-Stelzmann-Str. 26
50931 Cologne
Introduction
Transcription by RNA Polymerase-II (Pol-II) is a highly controlled process. However, despite elaborate quality control mechanisms it is not error free. The fidelity of Pol-II declines with age resulting in increased elongation speed, increasing numbers of splicing mistakes and possibly increasing numbers of ‘transcriptional mistakes’, i.e. misincorporation of nucleotides in the mRNA molecule. In order to explore the physiological consequences for aging and disease we require new technologies that allow us to identify and quantify transcriptional mistakes.
In this project we will develop methods for quantifying transcriptional mistakes based on single-cell RNA-sequencing protocols combined with newly developed bioinformatic methods. Our method will meet the technological challenge to distinguish transcriptional mistakes from technical errors during the sequencing process and DNA mutations. We are going to validate the method using single-cell data with known genomic variability. Subsequently, we will apply this technology to aging and age-associated disease models, including models of replicative senescence and the Hutchinson-Gilford progeria syndrome in order to study the emergence, origin and physiological consequences of transcriptional mistakes in vitro and in vivo.
Clinical Relevance
Errors during transcription elongation can induce proteotoxic stress and shorten cellular lifespan, activate oncogenic programs and affect cell fate. However, we do not yet fully understand to what extent those mistakes contribute to ageing- and disease phenotypes. Our project will reveal the physiological occurrence of these mistakes and their relevance for ageing and the related Hutchinson-Gilford progeria syndrome.
Lab Website
For more information, please visit the following page: Beyer Lab.
Affiliations - Andreas Beyer
Publications generated during 1/2023-12/2025 with CMMC affiliation
2024
- Frobel J and Hansel-Hertsch R (2024). The age-related decline of helicase function-how G-quadruplex structures promote genome instability. FEBS Lett 10.1002/1873-3468.14939.
- Leote AC, Lopes F, Beyer A. Loss of coordination between basic cellular processes in human aging. Nat Aging. 2024 Oct;4(10):1432-1445. doi: 10.1038/s43587-024-00696-y. Epub 2024 Sep 3. PMID: 39227753; PMCID: PMC11485205.
- Palikyras S, Sofiadis K, Stavropoulou A, Danieli-Mackay A, Varamogianni-Mamatsi V, Horl D, Nasiscionyte S, Zhu Y, Papadionysiou I, Papadakis A, Josipovic N, Zirkel A, O'Connell A, Loughran G, Keane J, Michel A, Wagner W, Beyer A, Harz H, Leonhardt H, Lukinavicius G, Nikolaou C and Papantonis A (2024). Rapid and synchronous chemical induction of replicative-like senescence via a small molecule inhibitor. Aging Cell 10.1111/acel.14083: e14083.
- Papantonis A, Antebi A, Partridge L, Beyer A. Age-associated changes in transcriptional elongation and their effects on homeostasis. Trends Cell Biol. 2024 Dec 19:S0962-8924(24)00247-2. doi: 10.1016/j.tcb.2024.11.005. Epub ahead of print. PMID: 39706758.
- Sauer PV, Pavlenko E, Cookis T, Zirden LC, Renn J, Singhal A, Hunold P, Hoehne-Wiechmann MN, van Ray O, Kaschani F, Kaiser M, Hansel-Hertsch R, Sanbonmatsu KY, Nogales E and Poepsel S (2024). Activation of automethylated PRC2 by dimerization on chromatin. Mol Cell 84(20): 3885-3898 e3888.
- Unger Avila P, Padvitski T, Leote AC, Chen H, Saez-Rodriguez J, Kann M, and Beyer A (2024). Gene regulatory networks in disease and ageing. Nat Rev Nephrol. doi:10.1038/s41581-024-00849-7.
2023
- Debes C, Papadakis A, Gronke S, Karalay O, Tain LS, Mizi A, Nakamura S, Hahn O, Weigelt C, Josipovic N, Zirkel A, Brusius I, Sofiadis K, Lamprousi M, Lu YX, Huang W, Esmaillie R, Kubacki T, Spath MR, Schermer B, Benzing T, Muller RU, Antebi A, Partridge L, Papantonis A, and Beyer A (2023). Ageing-associated changes in transcriptional elongation influence longevity. Nature 616, 814-821. doi:10.1038/s41586-023-05922-y.
- Kreer C, Lupo C, Ercanoglu MS, Gieselmann L, Spisak N, Grossbach J, Schlotz M, Schommers P, Gruell H, Dold L, Beyer A, Nourmohammad A, Mora T, Walczak AM, and Klein F (2023). Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals. Nat Commun 14, 7137. doi:10.1038/s41467-023-42906-y.