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Research in the Jacobson laboratory is focused on cytoplasmic aspects of post-transcriptional regulation, namely translation termination, nonsense-mediated mRNA decay (NMD), and therapeutic nonsense suppression. Work from the lab indicates that premature and normal termination differ mechanistically, with premature termination being a relatively inefficient process that leads to the ribosomal recruitment of at least three key regulatory proteins (Upf1, Upf2/Nmd2, and Upf3). These factors appear to play a role in both the triggering of NMD and the dissociation of the premature termination complex. Current studies are attempting to: a) define the timing and interaction-dependencies of Upf1, Upf2/Nmd2, and Upf3 association with prematurely terminating ribosomes, b) evaluate the functional differences of normal vs. premature termination, and c) elucidate several different mechanisms by which a near cognate tRNA can be inserted into a ribosomal A site programmed with a nonsense codon. The latter process, nonsense suppression, is of particular interest as a potential pathway to treatment of the large number of human genetic disorders attributable to nonsense mutations.