Deadenylation

Deadenylation is the enzymatic shortening of the poly(A) tail at the 3' end of eukaryotic mRNAs. The length of the poly(A) tail influences mRNA stability and translational efficiency, with shorter tails generally associated with reduced translation and increased mRNA decay.

The two principal deadenylase systems in the cytoplasm are the CCR4-NOT complex and the PAN2-PAN3 complex. In CCR4-NOT, the catalytic deadenylases are CCR4 and CAF1 (also known as CNOT6/6L and CNOT7/8 in humans). The PAN2-PAN3 complex provides an initial phase of shortening in some transcripts. Additional deadenylases such as PARN participate in specific cellular contexts, including nuclear and cytoplasmic compartments. Deadenylation commonly proceeds until PABP binding is weakened, which facilitates decapping and subsequent 5' to 3' decay by XRN1 or 3' to 5' decay by the exosome.

Deadenylation plays a central role in mRNA turnover and translational control. For many transcripts, deadenylation is the rate-limiting step in decay. MicroRNA-mediated gene silencing often recruits CCR4-NOT to accelerate deadenylation via GW182/TNRC6, linking small RNA pathways to mRNA destabilization. In addition to cytoplasmic decay, deadenylation participates in nuclear RNA surveillance and processing in some contexts.

Regulation of deadenylation is cell-type and condition dependent, influenced by developmental cues, stress responses, and signaling pathways. Proper control of deadenylation is essential for normal gene expression, and its dysregulation has been associated with various diseases, including cancer and neurodegenerative disorders.