Research in our laboratory aims to understand principles by which RNA protein complexes (RNPs) change conformation and composition. Such dynamic changes of RNPs play a central role in RNA metabolism und are thus essential for cellular function.

We focus on the role(s) and the mechanism(s) of the central and ubiquitous driving forces behind RNP dynamics, the DExH/D "RNA helicases". These proteins are the largest group of enzymes in eukaryotic RNA metabolism. Virtually all aspects of RNA processing and function involve members of this protein family.

DExH/D proteins utilize ATP hydrolysis to catalyze conformational changes in RNA protein complexes. We seek to understand how these enzymes accomplish this essential biological feat. We are specifically interested in elucidating the molecular design that enables these proteins to couple the hydrolysis of ATP to changes in RNA or RNP complexes. In addition, we are investigating how DExH/D proteins function as parts of larger macromolecular assemblies. To address these questions, we utilize an interdisciplinary approach that includes molecular biology, biochemistry, bioinformatics, and novel single molecule biophysics.

We have shown that DExH/D proteins DExH/D proteins can directly rearrange RNP complexes and that RNP remodeling is based on the action of DExH/D proteins on single stranded RNA, not on unwinding of RNA secondary structure.

We have also demonstrated that DExH/D proteins can be selective towards particular RNP substrates, although this feature depends also on the RNP that is being remodeled. Finally, we have shown that certain DExH/D proteins can function as proofreaders that ensure correct conformations of RNPs.

We are now working to elucidate how the molecular design of DExH/D proteins enables these enzymes to catalyze RNP rearrangements and how these enzymes function in their physiological environment. We have also started to quantitatively investigate the mechanism of cap-dependent eukaryotic translation initiation. This dynamic RNP assembly, which can be reconstituted in vitro, provides a paradigm for a dynamic physiological RNA-protein complex that also contains DExH/D proteins.

Primer on DExH/D proteins