Ralf-Peter Jansen

mRNA Localization and Localized Translation

University of Tübingen
Faculty in: IMPRS

Portrait of Ralf Peter Jansen in front of a microscope.

Vita

Diploma in Biology 1989, Ruhr-Universität Bochum
PhD work 1989-1993 at EMBL, Heidelberg
Postdoctoral Training at Institute for Molecular Pathology
(IMP), Vienna
Professor of Biochemistry at GeneCenter Munich, 2003-2008
Professor of Biochemistry at the IFIB, University of Tuebingen since 2008

Microscopic image of a mouse fibroblast cell with fluorescent mRNA located at the migrating end of the cell. — Figure 1. ß-actin mRNA localizes to the migrating end of mouse fibroblast cells. Individual mRNPs (arrows) are detected by a fusion of GFP, the biotin ligase BirA*, and a viral coat protein (MCP), which is directed to the ß-actin mRNA via MS2 stem loops in the 3’-UTR of the mRNA.

Figure 1. ß-actin mRNA localizes to the migrating end of mouse fibroblast cells. Individual mRNPs (arrows) are detected by a fusion of GFP, the biotin ligase BirA*, and a viral coat protein (MCP), which is directed to the ß-actin mRNA via MS2 stem loops in the 3’-UTR of the mRNA.

Research Interest
Localization of mRNAs and local protein synthesis contribute to asymmetric protein distribution, cell fate determination and neuronal function. Like translation or decay, mRNA localization is controlled by RNA-binding proteins (RBPs) or miRNAs. One aspect of our work is the functional characterization of known, novel, or unconventional RNA-binding proteins that act at organelle membranes, mainly using budding yeast as model. In mammalian cells, we study the composition of mRNA and protein complexes (mRNPs), using proximity labeling (BioID) as well as combinations of RNA live imaging and single-molecule FISH.

Microscopic images of cells. — Figure 2. Loss of the ribosome-associated RBP Scp160 results in reduced aggregation of huntingtin-derived polyQ reporter proteins. Upper panels show scp160∆ cells, lower panels show wildtype cells expressing polyQ-mCherry.

Figure 2. Loss of the ribosome-associated RBP Scp160 results in reduced aggregation of huntingtin-derived polyQ reporter proteins. Upper panels show scp160∆ cells, lower panels show wildtype cells expressing polyQ-mCherry.

A second line of projects deals with the question how certain polyribosome-associated RBPs influence the translation of mRNAs and the function of the encoded proteins, especially in the case of aggregation-prone proteins like those found in polyQ-expansion related disorders. Using yeast as a tool, we study if and how these RBPs affect translation of specific transcripts, and how they influence folding of the proteins. We apply combinatorial approaches including imaging as well as low- and high-throughput protein analysis.

Available PhD Projects

Establishment of background-free RNA proximity labelling for low abundant RNA-protein complexes

Selected Reading

Cheng, M.H.K., Hoffmann, P.C., Franz-Wachtel, M., Sparn, C., et al. (2018). The RNA-binding protein Scp160p facilitates aggregation of many endogenous Q/N-rich proteins. Cell Reports 24, 20-26.
Mukherjee, J., Hermesh, O., Eliscovich, C., Nalpas, N., et al. (2019). beta-actin mRNA interactome mapping by proximity biotinylation. PNAS 116, 12863-12872.
Manchalu, S., Mittal, N., Spang, A. and Jansen, R.-P. (2014). Local translation of yeast ERG4 mRNA at the endoplasmic reticulum requires the brefeldin A resistance protein Bfr1. RNA 25, 1661–1672.