Prof. Dr. Sabine Rospert
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:
- 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.: 13563
- Cotranslational intersection between the SRP and GET targeting pathways to the ER of Saccharomyces cerevisiae.
Zhang Y, Schaffer T, Wölfle T, Fitzke E, Thiel G, Rospert S (2016).
Mol Cell Biol 36:2374-2383
- 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
- Release factor eRF3 mediates premature translation termination on polylysine-stalled ribosomes in Saccharomyces cerevisiae.
Chiabudini M, Tais A, Zhang Y, Hayashi S, Wölfle T, Fitzke E, Rospert S (2014).
Mol Cell Biol 34: 4062-4076
- Inefficient SRP Interaction with a Nascent Chain Triggers a mRNA Quality Control Pathway.
Karamyshev AL, Patrick AE, Karamysheva ZN, Griesemer DS, Hudson H, Tjon-Kon-Sang S, Nilsson I, Otto H, Liu Q, Rospert S, Heijne G, Johnson AE, Thomas PJ (2014)
Cell 156: 146-157
- Transcriptional activation of Polycomb-repressed genes by ZRF1.
Richly H, Rocha-Viegas L, Ribeiro JD, Demajo S, Gundem G, Lopez-Bigas N, Nakagawa T, Rospert S, Ito T, Di Croce L (2010)
Nature 468: 1124-1128
- A signal-anchor sequence stimulates signal recognition particle binding to ribosomes from inside the exit tunnel.
Berndt U, Oellerer S, Zhang Y, Johnson AE, Rospert S (2009)
Proc Natl Acad Sci U S A 106: 1398-1403
- The Hsp70 homolog Ssb is essential for glucose sensing via the SNF1 kinase network.
von Plehwe U, Berndt U, Conz C, Chiabudini M, Fitzke E, Sickmann A, Petersen A, Pfeifer D, Rospert S (2009)
Genes Dev 23: 2102-2115
- The Hsp70 Ssz1 modulates the function of the ribosome-associated J-protein Zuo1.
Huang P, Gautschi M, Walter W, Rospert S, Craig EA (2005)
Nat Struct Mol Biol 12: 497-504
- The chaperones MPP11 and Hsp70L1 form the mammalian ribosome-associated complex.
Otto H, Conz C, Maier P, Wölfle T, Suzuki CK, Jenö P, Rücknagel P, Stahl J, Rospert S (2005)
Proc Natl Acad Sci USA 102: 10064-10069