Biology

Prof. Dr. Ralf Ficner
Department of Molecular Structural Biology, Georg-August-University Goettingen, Germany

Maturation of RNA transcripts may include multiple steps like splicing, modification, and editing. DEAH-box RNA helicases are found in all kingdoms of life and they are required for many processes like pre-mRNA splicing or ribosome maturation, however, their exact modus operandi is still elusive. We have determined crystal structures of the spliceosomal DEAH-box proteins Prp43 and Prp2 in different functional states (ADP, ATP, ATP-RNA) and of a complex of Prp2 with its activating G-patch protein Spp2. The analysis of these structures and the characterization of various novel mutants provide insights into the mechanisms of RNA loading and unwinding.

tRNAs of all organisms contain a large number of modified nucleosides. In prokaryotes and archae tRNA stability as well as cellular UV protection relies on the post-transcriptional modification of uracil at position 8 to 4-thiouridine. The crystal structure analysis of the 4-thioruidine synthetase in complex with a truncated tRNA revealed the structural basis for the specificity of tRNA U8 thiolation. The THUMP domain of the enzyme recognizes the 3’-CCA end thereby positions the U8 in the catalytic center. We propose that this strategy of a molecular ruler is also applied by other THUMP domain containing tRNA-modifying enzymes.