Polyadenylate polymerase (PAP)

Polyadenylate polymerase (PAP) is a template-independent nucleotidyltransferase that catalyzes the addition of a poly(A) tail to the 3' end of messenger RNA (mRNA) precursors. This process, known as polyadenylation, is a fundamental step in eukaryotic gene expression, influencing mRNA stability, transport from the nucleus to the cytoplasm, and translation efficiency (UniProt P51003). In the context of oncology, PAP isoforms such as PAPOLA (Neo-PAP) are frequently upregulated in various malignancies, including breast cancer and leukemia, where they support the rapid turnover and stabilization of transcripts required for cell proliferation (PubMed 10430911). Furthermore, viral polyadenylate polymerases are essential for the life cycle of many double-stranded DNA viruses, such as poxviruses, making them viable targets for antiviral drug development (PubMed 16280325). Therapeutic strategies often involve nucleoside analogs like cordycepin (3'-deoxyadenosine), which act as chain terminators during the polyadenylation process. This leads to the production of truncated, unstable mRNA and subsequent cell death, particularly in cancer cells that are highly dependent on rapid mRNA processing (PubMed 24333700). While targeting PAP offers a potent mechanism for inhibiting cell growth, challenges include achieving selectivity for viral or tumor-specific isoforms to minimize systemic toxicity in healthy tissues.

Other names

Polynucleotide adenylyltransferasePAPOLAPAP-alphaNeo-PAPPoly(A) polymerase alpha

Inhibition of polyadenylation through competitive binding or chain termination, leading to reduced mRNA stability and translation.