In eukaryotes, assembly of a ribosome on an mRNA (translation initiation) requires the action of at least 12 initiation factors and energy input from the hydrolysis of both ATP and GTP. Translation initiation is a key point in the control of gene expression and breakdown of proper initiation and its control play roles in a number of human diseases. Our lab uses a fully reconstituted yeast-based translation initiation system and a wide variety of biochemical and biophysical methods to dissect the molecular mechanics of this central biological process. We collaborate closely with geneticists and structural biologists in order to build a complete picture of the operation of the eukaryotic translational machinery. We are also developing chemical reagents to control translation initiation, with the hope that they may some day become drugs.
Publications:
L.A. Passmore, T.M. Schmeing, D. Maag, D.J. Applefield, M.G. Acker, M.A. Algire, J.R. Lorsch‡, V. Ramakrishnan‡ “The Eukaryotic Translation Initiation Factors eIF1 and eIF1A Induce an Open Conformation of the 40S Ribosome.” Mol Cell. (2007) 26: 41-50.
Pub Med Reference
Y.-N. Cheung, D. Maag, S. F. Mitchell, C. A. Fekete, M. A. Algire, J. E. Takacs, N. Shirokikh, T.V. Pestova, J. R. Lorsch‡, and A.G. Hinnebusch‡ “Dissociation of eIF1 from the 40S ribosomal subunit is a key step in start codon selection in vivo.” Genes and Dev. (2007) 21: 1217-1230.Pub Med Reference
M.G. Acker, S.E. Kolitz, S.F. Mitchell, J.S. Nanda and J. R. Lorsch “Reconstitution of yeast translation initiation.” Methods in Enzymology (2007), 430: 111-145.Pub Med Reference
M.G. Acker and J.R. Lorsch “Mechanism of ribosomal subunit joining during eukaryotic translation initiation.” Biochem Soc Trans. (2008) 36:653-7.Pub Med Reference
S.F. Mitchell and J.R. Lorsch “Should I stay or should I go? Eukaryotic translation initiation factors 1 and 1A control start codon recognition.” J Biol Chem. (2008) 283: 27345-9.Pub Med Reference
J. Dong, J.S. Nanda, H. Rahman, M.R. Pruitt, B.S. Shin, C.M. Wong, J.R. Lorsch, and A.G. Hinnebusch “Genetic identification of yeast 18S rRNA residues required for efficient recruitment of initiator tRNA(Met) and AUG selection.” Genes Dev. (2008) 22: 2242-55.Pub Med Reference
M.G. Acker, B.S. Shin, J.S. Nanda, A.K. Saini, T.E. Dever. and J.R. Lorsch “Kinetic analysis of late steps of eukaryotic translation initiation.” J. Mol. Biol. (2009) 385: 491-506.Pub Med Reference
S.E. Kolitz, J.E. Takacs and J.R. Lorsch “Kinetic and thermodynamic analysis of the role of start codon/anticodon base pairing during eukaryotic translation initiation.” RNA (2009) 15: 138-52.Pub Med Reference
