Molecular functions of deadenylases and their regulatory mechanisms in human diseases: A review

Deadenylases possess intrinsic 3' → 5' exoribonuclease activity, which specifically mediates the removal of poly(A) tails at the 3' terminus of mRNAs. As a key step in post-transcriptional mRNA processing, trimming excessive poly(A) tails to an appropriate length is critical for maintaining mRNA stability and translational efficiency. Structurally, nearly all deadenylases contain a conserved catalytic nuclease domain and are classified into the DEDD and EEP superfamilies according to the structural features of their catalytic domains. Functionally, these enzymes participate in diverse biological processes, including mRNA degradation, DNA damage response, maintenance of genomic stability, embryonic development, cellular metabolism, cell proliferation, cell cycle progression, and pluripotency regulation. Dysfunction of deadenylases compromises their capacity to remove mRNA poly(A) tails, leading to the disruption of post-transcriptional gene regulatory networks. Importantly, accumulating evidence further indicates that deadenylases are involved in the initiation and progression of a wide spectrum of pathological conditions, including telomere-related diseases, mitochondrial disorders, metabolic diseases, neurodegenerative diseases, cardiovascular diseases, reproductive disorders, and malignant tumors. In this review, we systematically summarize recent advances regarding deadenylases, with a focus on their biochemical and enzymatic properties, biological functions, and molecular mechanisms by which they contribute to human diseases. This summary aims to lay a theoretical foundation for the discovery and development of targeted therapies against deadenylase-associated diseases.