Centre for Biological Signalling Studies

Prof. Dr. Sabine Rospert

Prof. Dr. Sabine Rospert

Institute of Biochemistry and Molecular Biology, University of Freiburg

+49 761 203 5259


All newly synthesized polypeptides exit the ribosome through a tunnel in their large subunit. It is now recognized that nascent polypeptides interact with components of the exit tunnel and transmit information from within the tunnel to distant sites of the ribosome as well as to a growing list of ribosome-bound protein biogenesis factors (RPBs).

RPBs affect protein biogenesis in various ways. They can mediate de novo folding, targeting to cellular compartments, and they covalently modify nascent polypeptides. The specific set of RPBs recruited to a ribosome depends on the amino acid sequence of the nascent chain a ribosome is currently translating. How the dynamic process of RPB recruitment is organized chronologically and spatially is focus of our research.

RPBs, specifically of ones homologous to chaperones of the Hsp70 and Hsp40 families, not only function when bound to ribosomes, but also in the cytosol and in the nucleus. Here, RPBs are involved in the regulation of central signal transduction pathways, e.g. in the maintenance of energy homeostasis, or in transcriptional regulation, e.g. during development. In this context the chaperones mediate or prevent protein-protein interactions of folded client proteins. Recent evidence suggests that the interaction with the chaperones is regulated via posttranslational modifications in the client proteins. Mechanistic details of this novel RPB function and the question of whether or not the chaperones may coordinate protein synthesis with transcriptional programs and/or energy metabolism are unknown. We aim to understand how the interplay between components of the eukaryotic ribosome, nascent chains, and RPBs is coupled to the ribosome-independent functions of RPBs in the cytosol and in the nucleus.


10 selected publications:

  • Ribosome-bound Get4/5 facilitates the capture of tail-anchored proteins by Sgt2 in yeast.
    Zhang Y, De Laurentiis E, Bohnsack KE, Wahlig M, Ranjan N, Gruseck S, Hackert P, Wölfle T, Rodnina MV, Schwappach B, Rospert S (2021).
    Nat Commun. 12(1):782.
  • The ribosome-associated complex RAC serves in a relay that directs nascent chains to Ssb.
    Zhang Y, Valentín Gesé G, Conz C, Lapouge K, Kopp J, Wölfle T, Rospert S, Sinning I (2020).
    Nat Commun. 11(1):1504.
  • Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.
    Puleston DJ, Buck MD, Klein Geltink RI, Kyle RL, Caputa G, O'Sullivan D, Cameron AM, Castoldi A, Musa Y, Kabat AM, Zhang Y, Flachsmann LJ, Field CS, Patterson AE, Scherer S, Alfei F, Baixauli F, Austin SK, Kelly B, Matsushita M, Curtis JD, Grzes KM, Villa M, Corrado M, Sanin DE, Qiu J, Pällman N, Paz K, Maccari ME, Blazar BR, Mittler G, Buescher JM, Zehn D, Rospert S, Pearce EJ, Balabanov S, Pearce EL (2019).
    Cell Metab. 30(2):352-363.e8.
  • A dual role of the ribosome-bound chaperones RAC/Ssb in maintaining the fidelity of translation termination.
    Gribling-Burrer AS, Chiabudini M, Zhang Y, Qiu Z, Scazzari M, Wölfle T, Wohlwend D, Rospert S (2019).
    Nucleic Acids Res. 47(13):7018-7034
  • The yeast Hsp70 homolog Ssb: a chaperone for general de novo protein folding and a nanny for specific intrinsically disordered protein domains.
    Hübscher V, Mudholkar K, Rospert S (2017).
    Curr Genet. 63(1):9-13.
  • The Hsp70 homolog Ssb affects ribosome biogenesis via the TORC1-Sch9 signaling pathway.
    Mudholkar K, Fitzke E, Prinz C, Mayer MP, Rospert S (2017).
    Nat Commun. 8(1):937.
  • Two chaperones locked in an embrace: structure and function of the ribosome-associated complex RAC.
    Zhang Y, Sinning I, Rospert S (2017).
    Nat Struct Mol Biol. 24(8):611-619
  • Interaction of the cotranslational Hsp70 Ssb with ribosomal proteins and rRNA depends on its lid domain.
    Gumiero A, Conz C, Gesé GV, Zhang Y, Weyer FA, Lapouge K, Kappes J, von Plehwe U, Schermann G, Fitzke E, Wölfle T, Fischer T, Rospert S*, Sinning I* (2016).
    Nat Commun *co-corresponding
  • The Hsp70 homolog Ssb and the 14-3-3 protein Bmh1 jointly regulate transcription of glucose repressed genes in Saccharomyces cerevisiae.
    Hübscher V, Mudholkar K, Chiabudini M, Fitzke E, Wölfle T, Pfeifer D, Drepper F, Warscheid B, Rospert S (2016).
    Nucleic Acids Res 44: 5629-5645
  • Cotranslational Intersection between the SRP and GET Targeting Pathways to the Endoplasmic Reticulum of Saccharomyces cerevisiae.
    Zhang Y, Schäffer T, Wölfle T, Fitzke E, Thiel G, Rospert S (2016).
    Mol Cell Biol. 36(18):2374-83.