Poly (A)-specific ribonuclease (PARN) is an enzyme that catalyzes deadenylation, the removal of adenosine residues from the poly(A) tail of mRNA. This process is the first and crucial step in mRNA degradation, thus regulating mRNA stability. PARN also plays roles in various biological processes such as embryogenesis, oocyte maturation, cell-cycle progression, telomere biology, non-coding RNA maturation and ribosome biogenesis [1].

In pancreatic β cells, Parn conditional knockout mice showed reduced glucose-stimulated insulin secretion (GSIS) despite normal β-cell development and insulin sensitivity. Transcriptomic analyses revealed abnormal mRNA expression of genes vital for insulin secretion in PARN-deficient β cells. PARN was found to interact with polypyrimidine tract-binding protein 1 (PTBP1), regulating the RNA stability of Slc30a8 and Chst3. Interference with either PARN or PTBP1 disrupted this stability, indicating that PARN deficiency hampers GSIS and insulin maturation by destabilizing Slc30a8 and Chst3 RNAs [2].

In glioblastoma stem cells (GSCs), PARN depletion reduced infiltration and prolonged survival in orthotopic brain tumor xenografts. PARN positively regulated self-renewal and proliferation of GSCs through its 3'-5' exoribonuclease activity by modulating EGFR-STAT3 signaling [3].

In conclusion, PARN is essential for regulating mRNA stability and is involved in multiple biological processes. The use of Parn KO/CKO mouse models has revealed its significance in diseases such as diabetes-related pancreatic β-cell function impairment and glioblastoma, providing insights into potential therapeutic targets for these conditions.