Control of mRNA metabolism by deadenylation

Abstract

The presence of a polyadenosine tail is an important determinant of mRNA translation and stability. The regulated removal of the tail, i.e. deadenylation, leads to either translational quiescence or mRNA degradation. Deadenylation, therefore, is a critical node in gene expression and is especially important in certain biological contexts such as in the early embryo and in neurons. All mRNAs deadenylate at different rates; some fast, some slow. In addition, deadenylation is enhanced by message‐specific regulatory factors. For instance, many 3’ UTR binding proteins and the miRNA machinery drive post‐transcriptional regulation (in part) by facilitating deadenylation. Despite the importance of deadenylation, little is known about how differential rates of poly(A) tail shortening are achieved. One clue comes from studies that show that mRNA translation rates are intimately connected to deadenylation rate. Our recent work has begun to tease out the complex molecular details that intertwine translation and deadenylation. Moreover, we have concentrated on understanding the function of protein factors that facilitate removal of the poly(A) tail. Deadenylation is catalyzed by the CCR4‐NOT protein complex. The function of distinct members of this complex as well as how these factors influence rates of deadenylation will be discussed.