PhD, Group Leader at the Max Planck Institute for Biophysical Chemistry
- Ph.D., The Ohio State University, Columbus, OH, USA (1996)
- Post-Doc, Max-Planck-Institute for Biochemistry, Martinsried, Germany (1997-2002)
- Habilitation and Privatdozentur, Technical University München, Faculty of Chemistry, München, Germany (2002)
- Group leader, Max Planck Institute for Biophysical Chemistry (since 2002)

Major Research Interests
Gene expression pathways encompass a number of RNA metabolic steps such as transcription, splicing, editing, post-transcriptional nucleotide modification, nuclear export, RNA surveillance, cytoplasmic localization, translation and RNA degradation, each of which is orchestrated by a multi-component cellular machinery. In recent years it became evident that the various machineries are extensively interconnected and that the route of a given RNA through this network of processes is determined by its particular set of decorating proteins, RNAs or RNA-protein complexes. The general interest of our group lies in exploring the molecular mechanisms underlying the modes of action and functional coupling of RNA-protein machineries involved in these gene expression networks. In particular, we are interested in the inner workings of the spliceosome, the multi-megadalton RNA-protein enzyme that removes non-coding intervening sequences from precursor-messenger RNAs and concomitantly ligates the neighboring coding regions. We employ X-ray crystallography to elucidate the atomic structures of proteins, RNAs and macromolecular complexes, which are part of these molecular machines. Structure-guided hypotheses are then tested by biochemical, biophysical, molecular biological and genetics approaches.





Figure: The crystal structure of a ternary complex comprising a central fragment of human (h) Prp31 protein (blue), 15.5K protein (red) and a 5'-stem loop (SL; gold) of U4 small nuclear RNA revealed how hPrp31 binds to a composite RNA-protein binding platform assembled from parts of 15.5K and the U4 5'-SL (Liu et al., 2007). hPrp31 binds to one region of this binding platform by a lock-and-key type mechanism, while it recognizes another region of the RNA via an induced fit strategy (B). The structure explains the strictly ordered binding of the two proteins to the RNA, with 15.5K binding before hPrp31. Furthermore, it elucidates the mechanism, by which hPrp31 can act as a molecular ruler, which discriminates non-cognate binding platforms via the different lengths in one of the RNA stems (C).

Homepage Department/Research Group:
http://www.chemie.fu-berlin.de/cgi-bin/personen_en?Markus+Wahl

Selected Recent Publications
- Mukherjee K, Sharma M, Urlaub H, Bourenkov GP, Jahn R, Südhof TC, Wahl MC (2008) CASK Functions as a Mg2+-Independent Neurexin Kinase. Cell 133: 328-339

- Ganichkin OM, Xu X-M, Carlson BA, Mix H, Hatfiled DL, Gladyshev VN, Wahl MC (2008) Structure and catalytic mechanism of eukaryotic selenocysteine synthase. J. Biol. Chem. 283: 5849-5865

- Liu S, Li P, Dybkov O, Nottrott S, Hartmuth K, Lührmann R, Carlomagno T, Wahl MC (2007) Binding of the human Prp31 Nop domain to a composite RNA-protein platform in U4 snRNP. Science 316: 115-120

- Pena V, Liu S, Bujnicki JM, Lührmann R, Wahl MC (2007) Structure of a multipartite protein-protein interaction domain in splicing factor Prp8 and its link to Retinitis pigmentosa. Mol. Cell 25: 615-624

- Diaconu M, Kothe U, Schlünzen F, Fischer N, Harms JM, Tonevitsky A, Stark H, Rodnina MV, Wahl MC (2005) Structural basis for the function of the ribosomal L7/12 stalk in factor binding and GTPase activation. Cell 121: 991-1004