A Conversation with Lynne Maquat.

Abstract

Dr. Maquat: In human diseases of the type that we studied, translation of an mRNA terminates prematurely. The disease-associated mutation is either a frameshift or a nonsense mutation that generates a premature termination codon, which, when recognized by a ribosome, triggers decay of the mRNA. This is a good thing in the sense that if a cell were to make truncated proteins, these proteins could be toxic. The open reading frame of the mutated mRNA is abnormally short, and therefore the encoded protein would be truncated, with the potential to gum up the cellular machine it works in. We figured out the rules for how a cell differentiates a normal termination codon, which generally doesn’t trigger mRNA decay, from a premature termination codon, which generally does.