Allan S. Jacobson

Jacobson's research has addressed the post-transcriptional regulation of gene expression. He demonstrated that the mRNA poly(A) tail enhances translation initiation, and formulated the closed-loop mRNP model fundamental for understanding multiple aspects of cytoplasmic post-transcriptional regulation in eukaryotes. Jacobson established a yeast system to analyze the regulation of mRNA decay and identified and elucidated the nonsense-mediated mRNA decay (NMD) pathway, its substrates, the roles of the Upf proteins in NMD regulation, and the cellular utilization of NMD as a probabilistic quality control mechanism capable of detecting errors during protein synthesis. He defined novel regulatory functions of the mRNA decapping enzyme, showing that decapping activators bind distinct Dcp2 domains to provide substrate specificity. He demonstrated that premature and normal translation termination differed mechanistically, with premature termination being a less efficient process, and co-founded a company (PTC Therapeutics Inc.) that exploited this difference to develop a first-in-class drug (ataluren/Translarna) for the treatment of inherited disorders caused by nonsense mutations. The latter drug is currently approved for the treatment of nonsense mutation Duchenne Muscular Dystrophy patients in the EU.