Deadenylation is the exoribonucleolytic shortening of eukaryotic poly(A) tails. 
It is often the first and rate-limiting step for mRNA decay and translational 
silencing. The process is catalysed by a diversity of deadenylases, which 
provide robust and flexible means to control mRNA levels and gene expression. 
Poly(A)-specific ribonuclease (PARN) is a major mammalian deadenylase and the 
only known to concurrently bind the 5' cap-structure and the 3' poly(A), thus 
enhancing the degradation rate and amplifying its processivity. PARN is 
important during oocyte maturation, embryogenesis, early development, DNA 
damage, and in cell-cycle progression, but also in processes beyond mRNA 
metabolism, such as the maturation of snoRNAs. The enzyme also participates in 
nonsense-mediated mRNA decay and in the regulation of cytoplasmic 
polyadenylation. Importantly, PARN is involved in the degradation of several 
cancer-related genes, while its expression is altered in cancer. Apart from the 
direct interaction with the cap structure, several strategies regulate PARN 
activity, such as phosphorylation, interaction with RNA-binding proteins (RBPs), 
and natural nucleotides. Recent studies have focused on the regulation of its 
activity by synthetic nucleoside analogues with therapeutic potential. In this 
context, the wide repertoire of RBPs and molecules that regulate PARN activity, 
together with the established role of deadenylases in miRNA-mediated regulation 
of mRNA expression, suggest that mRNA turnover is more complex than it was 
previously thought and PARN holds a key role in this process. In this review, we 
highlight the importance of PARN during RNA's lifecycle and discuss clinical 
perspectives of modulating its activity.