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Petra Beli

Cellular responses to transcription and translation stress

Human cells are exposed to stress induced by pollutants from the environment, as well as compounds generated during normal metabolism, such as reactive aldehydes. Ageing of organisms is accompanied by a deterioration of proteome homeostasis, which is characterised by an accumulation of nonfunctional proteins and deregulated cellular responses to stress. At the molecular level, aged cells show alterations in the elongation rate of RNA polymerase and increased stalling of ribosomes; however, the physiological mediators underlying these phenomena remain unclear. Moreover, it is poorly understood what cell-protective mechanisms are in place to cope with transcription and translation stress, and how these are remodelled during ageing.

In the Beli lab, we are interested in understanding transcription- and translation-coupled quality control mechanisms that maintain the fidelity of gene expression and protein synthesis. To achieve these goals, we use quantitative mass spectrometry-based proteomics to investigate cellular responses to stress that cause damage to genomic DNA and transcribed RNA. Our studies focus on components of the ubiquitin system that regulate cellular responses to stress by catalysing different types of ubiquitin chains on substrate proteins. We characterise ubiquitin-based mechanisms and ubiquitin E3 ligases that protect aged cells from the deleterious effects of chronic transcription and translation stress.

Research website

Positions held

  • Since 2020: Adjunct Director, Institute of Molecular Biology (IMB) and Full Professor, Faculty of Biology, Johannes Gutenberg University (JGU), Mainz
  • Since 2013: Emmy Noether Group Leader, Institute of Molecular Biology (IMB), Mainz
  • 2010 - 2013: Postdoctoral Researcher, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen

Education

  • 2011: PhD in Biology, Goethe University Frankfurt
  • 2007: Masters in Molecular Biology, University of Zagreb

Selected publications by Petra Beli

Mosler T*, Baymaz HI*, Gräf JF, Mikicic I, Blattner G, Bartlett E, Ostermaier M, Piccinno R, Yang J, Voigt A, Gatti M, Pellegrino S, Altmeyer M, Luck K, Ahel I, Roukos V and Beli P (2022) PARP1 proximity proteomics reveals interaction partners at stressed replication forks. Nucleic Acids Res, 50:11600–11618 (*indicates joint contribution) Link

Mosler T, Conte F, Longo GMC, Mikicic I, Kreim N, Möckel MM, Petrosino G, Flach J, Barau J, Luke B, Roukos V and Beli P (2021) R-loop proximity proteomics identifies a role of DDX41 in transcription-associated genomic instability. Nat Commun, 12:7314 Link

Hildebrandt A, Brüggemann M, Rücklé C, Boerner S, Heidelberger JB, Busch A, Hänel H, Voigt A, Möckel MM, Ebersberger S, Scholz A, Dold A, Schmid T, Ebersberger I, Roignant JY, Zarnack K#, König J# and Beli P# (2019) The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation. Genome Biol, 20:216 (#indicates joint correspondence) Link

Borisova ME, Voigt A, Tollenaere MAX, Sahu SK, Juretschke T, Kreim N, Mailand N, Choudhary C, Bekker-Jensen S, Akutsu M, Wagner SA and Beli P (2018) p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage. Nat Commun, 9:1017 Link

Heidelberger JB, Voigt A, Borisova ME, Petrosino G, Ruf S, Wagner SA and Beli P (2018) Proteomic profiling of VCP substrates links VCP to K6‐linked ubiquitylation and c‐Myc function. EMBO Rep, 19:e44754 Link