Fig. 2. Schematic of PABPN1 functions identified in metazoan cells and fission yeast.

In metazoan cells (top), PABPN1 (represented as blue circles) is implicated in functions within both the nucleus and the cytoplasm. Nuclear functions linked to PABPN1 include: (1) binding to the poly(A) tail of nascent mRNA transcripts to stimulate polyadenylation by the poly(A) polymerase (PAP) [9] in conjunction with the cleavage and polyadenylation specificity factor (CPSF); (2) modulating alternative polyadenylation through binding to and masking “weak” proximal cleavage/polyadenylation sites allowing the cleavage and polyadenylation machinery to assemble at distal “stronger” sites [12]; (3) following polyadenylation, accompanying the transcript to the nuclear pore complex (NPC) and directly or indirectly aiding in nuclear RNA export [11, 66]; (4) regulating the steady-state level of long non-coding RNAs (lncRNA) by mediating their turnover via the nuclear exosome [13]. In the cytoplasm, functions linked to PABPN1 include: (5) contributing to a pioneer round of translation that is vital for mRNA quality control [5] where the transcript is associated with the nuclear cap binding complex (CBC) consisting of CBC20 and CBC80 as well as the ribosome after which PABPN1 is replaced by cytoplasmic PABPC1; and (6) as identified only in Drosophila thus far, cytoplasmic deadenylation of transcripts via the CCR4-NOT complex [41]. In the fission yeast S. pombe (bottom), the nuclear poly(A) binding protein, Pab2, is involved in (7) processing of small nucleolar RNAs [46] and (8) turnover of meiotic transcripts via the nuclear exosome [49].