deadenylases

Deadenylases are a group of ribonucleases that remove poly(A) tails from eukaryotic mRNAs, a key step in regulating mRNA stability and translation. In many transcripts, shortening of the poly(A) tail destabilizes the molecule and promotes decay, either through 3' to 5' degradation by the exosome or after decapping followed by 5' to 3' decay.

The best-characterized deadenylases operate within multi-protein complexes. The CCR4-Not complex contains catalytic subunits such as CCR4 (CNOT6/CNOT6L) and CAF1 (CNOT7/CNOT8) and is a major cytoplasmic deadenylase in many organisms. The Pan2-Pan3 complex also contributes to deadenylation, with Pan2 providing catalytic activity and Pan3 acting as a regulator. Additional deadenylases include poly(A)-specific ribonuclease (PAR N), which can function in both the nucleus and cytoplasm, and other related exonucleases that target poly(A) tails under specific cellular contexts.

Deadenylation is often directed to specific transcripts by RNA-binding proteins and microRNA-induced silencing complexes, linking tail shortening to regulated gene expression. Once the poly(A) tail is shortened, interactions with poly(A)-binding protein and other decay factors determine whether translation is repressed, and which decay pathway is engaged.

Biological significance of deadenylases spans development, cell cycle control, stress responses, and differentiation. They are distributed primarily in the cytoplasm, with some forms localized to the nucleus, reflecting diverse roles in RNA turnover and gene expression regulation. Dysregulation of deadenylation has been associated with various diseases and cellular dysfunctions.