Deadenylase

Deadenylases are enzymes that catalyze the shortening or removal of poly(A) tails from messenger RNA (mRNA) in eukaryotic cells. The poly(A) tail influences mRNA stability and translational efficiency, and its shortening often precedes mRNA decay. Deadenylation is typically the first and rate-limiting step in cytoplasmic mRNA decay, after which decapping and exonucleolysis proceed.

The best-characterized deadenylation pathways involve multi-subunit complexes. The CCR4-NOT complex contains two catalytic deadenylases, CCR4 and CAF1, which shorten poly(A) tails in many transcripts. In mammals, these are encoded by CNOT6/CNOT6L (CCR4) and CNOT7/CNOT8 (CAF1). Another major pathway is the PAN2-PAN3 complex, where PAN2 provides catalytic activity and PAN3 serves as an adaptor. A separate enzyme, PARN (poly(A)-specific ribonuclease), operates on specific transcripts or under particular cellular conditions. Together these enzymes regulate tail length across diverse mRNAs and cellular contexts.

Functionally, deadenylation reduces binding of poly(A)-binding proteins, destabilizes the transcript, and promotes both 5′-to-3′ decapping and 3′-to-5′ exonuclease decay. Deadenylation also influences translation by modulating tail length and PABP interactions. Targeting of specific mRNAs is guided by RNA-binding proteins and microRNAs, often funneling transcripts to decay pathways or storage sites such as processing bodies.

Dysregulation of deadenylases has been linked to developmental defects and diseases, including cancer and neurological disorders. Because they act at the intersection of mRNA stability and translation, deadenylases are studied as key regulators of gene expression and potential therapeutic targets.