PABP

Poly(A)-binding proteins (PABP) are a family of RNA-binding proteins that recognize the poly(A) tail of eukaryotic mRNAs and regulate their stability and translation. The best-characterized member in many animals is PABPC1, but several paralogs exist in vertebrates (for example, PABPC3, PABPC4, PABPC5 in humans) and there are homologs in yeast (Pab1).

Structure and domains: PABPs typically feature multiple RNA recognition motifs (RRMs) in the N-terminal region that bind poly(A) sequences, and a C-terminal MLLE (PABC) domain that mediates protein–protein interactions. The RRMs bind the adenylate-rich tail, while the MLLE/PABC domain enables interactions with factors such as eIF4G, other initiation factors, and components of the mRNA decay machinery. Flexible linkers between these domains allow cooperative binding along the poly(A) tail.

Functions: Binding to the poly(A) tail helps circularize mRNA by promoting an interaction between the 5' cap complex and the poly(A) tail via eIF4G, thereby enhancing translation initiation. PABP also modulates mRNA stability by interacting with deadenylases and deadenylation complexes, influencing the length of the poly(A) tail and the decay rate. These activities are sensitive to poly(A) tail length, cellular conditions, and post-translational modifications, and they can be coordinated with microRNA pathways and other RNA-binding proteins.

Localization and evolution: In most contexts, cytoplasmic PABPs regulate translation in the cytoplasm, though some paralogs can shuttle between compartments. The PABP family is evolutionarily conserved across eukaryotes, with vertebrates harboring multiple paralogs and yeasts typically having a single essential Pab1. Nuclear poly(A)-binding proteins (such as PABPN1) perform related but distinct roles in polyadenylation and RNA processing.