mRNA Localization and Localized Translation

Ralf-Peter Jansen

RalfJansen23-11-2012-01 crop1
  • 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 since 2008

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 as well as combinations of RNA live imaging and single-molecule FISH.

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.

  • IMPRS 1-page GFP beta actin mef
    click to enlarge

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.

  • IMPRS-aggregates wt vs scp160
    click to enlarge

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.

Available PhD Projects

Identification of novel mRNA and lncRNA-associated proteins by proximity labeling (BioID).

Selected Reading

1) Jansen, R.-P., Niessing, D., Baumann, S. and Feldbrügge, M. (2014) mRNA transport meets membrane traffic. Trends in Genetics, 30, 408–417.

2) Hirschmann, W. D. et al. (2014) Scp160p is required for translational efficiency of codon-optimized mRNAs in yeast. Nucleic Acids Research 42, 4043–4055.

3) Genz, C., Fundakowski, J., Hermesh, O., Schmid, M. and Jansen, R.-P. (2013) Association of the Yeast RNA-binding Protein She2p with the Tubular Endoplasmic Reticulum Depends on Membrane Curvature. Journal of Biological Chemistry, 288, 32384–32393.

4) Roux, K. J. (2013) Marked by association: techniques for proximity-dependent labeling of proteins in eukaryotic cells. Cell. Mol. Life Sci. 70, 3657–3664.