PABPN1

PABPN1, or polyadenylate-binding protein nuclear 1, is a eukaryotic nuclear protein that binds poly(A) RNA and regulates the length of poly(A) tails added to mRNA during 3' end processing. In the nucleus, PABPN1 interacts with the cleavage and polyadenylation machinery, including poly(A) polymerase and CPSF, and stimulates tail elongation. Through its role in tail length control, PABPN1 influences mRNA stability, nuclear export, and translation, and it participates in aspects of RNA metabolism such as alternative polyadenylation.

Genetics and structure: The human PABPN1 gene encodes the PABPN1 protein, which contains an N-terminal polyalanine tract encoded by a GCN repeat. The tract normally contains a defined number of alanines, but expansion of this tract leads to disease. The polyalanine expansion is the basis of a well-characterized inherited disorder.

Clinical significance: The primary disorder associated with PABPN1 expansions is oculopharyngeal muscular dystrophy (OPMD). OPMD is typically autosomal dominant and presents in mid-adulthood with ptosis (drooping eyelids) and dysphagia, followed by progressive proximal muscle weakness. Muscle tissue from affected individuals often shows intranuclear inclusions containing mutant PABPN1. The disease is attributed to the toxic effects of the expanded protein and its tendency to form nuclear aggregates.

Expression and research: PABPN1 is widely expressed, with notable abundance in skeletal muscle. Given its central role in poly(A) tail biology, PABPN1 remains a focus of research into RNA processing and mechanisms underlying OPMD, including approaches aimed at reducing mutant PABPN1 expression or modulating polyadenylation.