Research in the Maeder Group
Research in the Maeder Lab centers on understanding the mechanisms involved in gene expression. The central dogma of biology says genetic information flows from DNA to RNA to protein in all living organisms. The precise manner of this information flow serves to regulate activation and repression of genes. Regulation of protein expression may occur at many levels along the information flow, from DNA to protein. A key early step in gene expression is pre-mRNA splicing. Initially, RNA transcribed from DNA has intervening non-protein coding sequences, or introns. The removal of introns must be precisely coordinated to avoid inaccuracies that can result in many diseases, including cancer and retinitis pigmentosa.
Splicing is facilitated by a large macromolecular complex of RNA and proteins called the spliceosome. The mechanism of pre-mRNA splicing involves large-scale rearrangements of protein-RNA complexes, which must be regulated to ensure both splicing timing and accuracy. My research focuses on understanding these large-scale rearrangements within the spliceosome. Specifically, our current focus is on understanding the role of RNA helicases and their interactions with other splicing components in the regulation of spliceosome assembly and diassembly.
We use a variety of biochemical, molecular biological, and genetics techniques to dissect the importance of protein-nucleic acid and protein-protein interactions in the spliceosome.
Abelson, J.*; Blanco, M.; Ditzler, M. A.; Fuller, F.; Aravamudhan, P.; Wood, M.; Villa, T.; Ryan, D. E.; Pleiss, J. A.; Maeder, C.; Guthrie, C.; Walter, N. G., Conformational dynamics of single pre-mRNA molecules during in vitro splicing. Nat Struct Mol Biol 2010, 17 (4), 504-12.
Maeder, C.‡; Kutach, A. K.‡; Guthrie, C.*, ATP-dependent unwinding of U4/U6 snRNAs by the Brr2 helicase requires the C terminus of Prp8. Nat Struct Mol Biol 2009, 16 (1), 42-8.
Featured in News & Views: Brow, D.A. Nat. Struct. Mol. Biol. 2009, 16(1): 7-8.
Featured in Cell Leading Edge Cell 2009,136(4): 571.
Zhang, L.; Xu, T.; Maeder, C.; Bud, L. O.; Shanks, J.; Nix, J.; Guthrie, C.; Pleiss, J. A.; Zhao, R.*, Structural evidence for consecutive Hel308-like modules in the spliceosomal ATPase Brr2. Nat Struct Mol Biol 2009, 16 (7), 731-9.