PABPN1
Domain
The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding.
Function
Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product (By similarity). Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length (By similarity). Increases the affinity of poly(A) polymerase for RNA (By similarity). Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes (PubMed:11371506). Binds to poly(A) and to poly(G) with high affinity (By similarity). May protect the poly(A) tail from degradation (By similarity). Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484).
Involvement in disease
Oculopharyngeal muscular dystrophy 1
OPMD1
An autosomal dominant, late-onset, slowly progressive myopathy characterized by eyelid ptosis, dysphagia and, sometimes by other cranial and limb-muscle involvement.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Arginine dimethylation is asymmetric and involves PRMT1 and PRMT3. It does not influence the RNA binding properties (By similarity).
Tissue Specificity
Ubiquitous.
Cellular localization
- Nucleus
- Cytoplasm
- Nucleus speckle
- Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Shuttles between the nucleus and the cytoplasm but predominantly found in the nucleus (PubMed:10688363). Its nuclear import may involve the nucleocytoplasmic transport receptor transportin and a RAN-GTP-sensitive import mechanism (By similarity). Is exported to the cytoplasm by a carrier-mediated pathway that is independent of mRNA traffic. Colocalizes with SKIP and poly(A) RNA in nuclear speckles (By similarity). Intranuclear filamentous inclusions or 'aggregates' are detected in the myocytes of patients; these inclusions contain PABPN1, ubiquitin, subunits of the proteasome and poly(A) RNA.
Alternative names
PAB2, PABP2, PABPN1, Polyadenylate-binding protein 2, PABP-2, Poly(A)-binding protein 2, Nuclear poly(A)-binding protein 1, Poly(A)-binding protein II, Polyadenylate-binding nuclear protein 1, PABII