deadenylylate

Deadenylylate, or deadenylation, refers to the enzymatic shortening or removal of the poly(A) tail from eukaryotic messenger RNA. This post-transcriptional modification is a major control point for mRNA stability and translation, and it often marks transcripts for decay. The process is carried out by specific deadenylase enzymes that hydrolyze the adenine residues of the poly(A) tail.

The best-characterized deadenylases act within multi-subunit complexes. In many organisms, the CCR4-NOT complex is the principal deadenylase. Its catalytic subunits include CCR4 (such as CNOT6 or CNOT6L in mammals) and CAF1 (CNOT7), which remove adenosines from the tail. Another important deadenylase is Pan2-Pan3, which can initiate deadenylation in the cytoplasm. The cytoplasmic deadenylase PARN also contributes in specific tissues or conditions, while nuclear deadenylation involves additional factors depending on the context.

Shortening of the poly(A) tail reduces binding of the poly(A)-binding protein (PABP), destabilizes the mRNA, and frequently directs decay through either 3' to 5' exonucleases/ the exosome or after decapping to 5' to 3' decay. Deadenylation can also repress translation independently of decay by impairing ribosome recycling. In many regulatory scenarios, microRNAs and associated effector proteins recruit deadenylases to target transcripts, linking deadenylation to post-transcriptional gene silencing.

Biological relevance includes development, differentiation, stress responses, and circadian regulation. Disruptions in deadenylation pathways have been associated with altered gene expression and, in some cases, disease. Methods to study deadenylation include poly(A) tail assays and high-throughput sequencing approaches that quantify tail length dynamics.