polyadenylate-binding protein 2; poly(A)-binding protein 2; polyadenylate-binding nuclear protein 1; nuclear poly(A)-binding protein 1 (PABPN1, PAB2, PABP2)

Function

• role in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nucleotides to the upstream cleavage product
• stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction & controls also the poly(A) tail length
• increases the affinity of poly(A) polymerase for RNA
• also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking & nonsense-mediated mRNA decay
• cooperates with SKIP to synergistically activate E-box- mediated transcription through MYOD1 & may regulate expression of muscle-specific genes
• binds to poly(A) & to poly(G) with high affinity
• may protect the poly(A) tail from degradation (putative)
• Arg dimethylation is asymmetric & involves PRMT1 & PRMT3; it does not influence the RNA binding properties
• binds RNA as a monomer & oligomerizes when bound to poly(A)
• interacts with PAPOLA, but only in presence of oligo(A) RNA
• interacts with transportin
• association in a ternary complex with CPSF4 & influenza A virus NS1 blocks pre-mRNAs processing, thereby preventing nuclear export of host cell mRNAs
• associates in a single complex with SKIP & MYOD1 & interacts with SKIP in differentiated myocytes.
• interacts with NUDT21/CPSF5

Structure

• monomer & homooligomer
• the RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding (putative)
• contains 1 RRM domain (RNA recognition motif)

Compartment

• nucleus (putative)
• cytoplasm
• shuttles between the nucleus & the cytoplasm but predominantly found in the nucleus
• its nuclear import may involve the nucleocytoplasmic transport receptor transportin & a RAN-GTP-sensitive import mechanism
• exported to the cytoplasm by a carrier-mediated pathway that is independent of mRNA traffic
• nucleus; nuclear speckle
• colocalizes with SKIP & poly(A) RNA in nuclear speckles (putative)

Alternative splicing

named isoforms=2 may be due to a competing donor splice site

Expression

ubiquitous

Pathology

• defects in PABPN1 are the cause of oculopharyngeal muscular dystrophy
• see oculopharyngeal muscular dystrophy for discussion on molecular pathology of the disease

Polymorphism

• the poly-Ala region of PABPN1 is polymorphic (6-7 repeats) in the population & is expanded to 8-13 repeats in patients with oculopharyngeal muscular dystrophy
• compound heterozygotes for (GCG)9 mutation & a (GCG)7 allele result in earlier onset & more severe clinical manifestations of the disease

More general terms

• polyadenylate binding protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8106
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8106
• OMIM: https://mirror.omim.org/entry/164300
• OMIM: https://mirror.omim.org/entry/602279
• UniProt: http://www.uniprot.org/uniprot/Q86U42.html