Co-translational quality control in eukaryotic cells

Proteins are central to any living organism. To protect cells from dysfunctional and toxic, disease-causing proteins formed by aberrant translation, eukaryotic co-translational quality control pathways detect translation defects and remove aberrant protein products, together with associated faulty mRNA blueprints and sometimes faulty ribosomal components. Much is still unknown about the molecular mechanisms underlying co-translational quality control, and how these interact with other cellular machineries and with organismal health and life cycle. These are research objects in my group. We use sequencing-based methods, most prominently UV crosslinking and analysis of cDNA (CRAC), to study RNA-protein interactions, translation and RNA modification in the context of co-translational quality control. These techniques provide a unique toolbox to approach our key questions:

1. Which molecular interactions underlie co-translational quality control triggering and how are different targets distinguished?

2. How does co-translational quality control interact with cellular stress responses, translation regulation and RNA modification?

3. How does co-translational quality control work in neurons and does it change with ageing?

With our RNA-centred research, we want to make fundamental contributions to the understanding of co-translational quality control and its links to age-related neurodegenerative diseases, to ultimately inform efforts to cure, prevent or delay the onset of such diseases.

Positions held

Since 2020: Junior Professor, Institute of Pharmaceutical and Biomedical Sciences (IPBS), Johannes Gutenberg University Mainz

2015-2020: Postdoctoral Research Associate (EMBO Long-term Fellowship 2015-2017), University of Edinburgh

04-12/2014: Postdoctoral Researcher, Heidelberg University

Education

2014: PhD in Biology, Heidelberg University, Hartmut Hoffman-Berling International Graduate School of Molecular and Cellular Biology (HBIGS)

2009: M.Sc. in Molecular Biotechnology, Heidelberg University

2006: B.Sc. in Molecular Biotechnology, Heidelberg University

Awards and recognition

2016: ‘Förderpreis der Fachgruppe Biochemie’ , thesis prize of the Biochemistry Division of the
Society of German Chemists (GDCh).

2015: EMBO Longterm Fellowship

2011: 1 year HBIGS PhD Fellowship

Selected publications

M.L. Winz, L. Peil, T.W. Turowski, J. Rappsilber, D. Tollervey (2019) Molecular interactions between Hel2 and RNA supporting ribosome-associated quality controlNature Communications, 10(1), 563. Link

M.L. Winz, H. Cahová, G. Nübel, J. Frindert, K. Höfer, A. Jäschke (2017) Capture and sequencing of NAD-capped RNA sequences with NAD captureSeq. Nature Protocols, 12 (1), 122-149. Link

H. Cahová*, M.L. Winz*, K. Höfer*, G. Nübel, A. Jäschke (2015) NAD captureSeq indicates NAD as a bacterial cap for a subset of regulatory RNAs. Nature, 519:374- 377.
(*: equal contributions). Link

R. Hauenschild, L. Tserovski, K. Schmid, K. Thüring, M.L. Winz, S. Sharma, K.-D. Entian, L. Wacheul, D.L.J. Lafontaine, J. Anderson, J. Alfonzo, A. Hildebrandt, A. Jäschke, Y. Motorin, M. Helm (2015) The reverse transcription signature of N-1-methyladenosine in RNA-Seq is sequence dependent. Nucleic Acids Research, 43(20):9950-9964. Link