DSSS - Elisa Izaurralde Memorial Lecture

The first, and often rate-limiting, step of canonical mRNA decay is removal of the poly(A) tail. There are two conserved deadenylation complexes in eukaryotes: Pan2-Pan3 and Ccr4-Not. In a current model of deadenylation, Pan2-Pan3 removes the distal, and Ccr4-Not the proximal, part of the poly(A) tail. Deadenylation occurs in gene- and context-dependent manners to allow transcript-specific control of poly(A) tail lengths. This targeted deadenylation is important in many processes including the inflammatory response and early development. RNA adapter proteins are thought to target specific mRNAs for deadenylation by Ccr4-Not. Examples of RNA adapters are Pumilio/Puf, TTP/tristetraprolin and the microRNA-induced silencing complex (miRISC). Understanding how specific mRNAs are targeted for deadenylation has been a central question in the field of gene expression for many years. I will present our most recent work on deadenylation.