Figure 1.
Pioneer round of translation promotes the removal of EJC constituents and replacement of PABPN1 by PABPC1. Pioneer translation initiation complex is exported from the nucleus to the cytoplasm bound by (1) CBC, which consists of CBP80-CBP20 at the 5′ cap and functions not only in the export of spliced mRNA but also as a translation initiation factor; (2) EJCs, which generally contain eIF4AIII and the NMD factors UPF2 and UPF3X or UPF3, located ~20–25 nucleotides upstream of exon-exon junctions if the mRNA underwent splicing; and (3) PABPN1 and PABPC1 at the poly(A) tail. Other factors that typify the pioneer translation initiation complex include the eIF3 and eJF4G factors and IMPα (not shown; see Fig. 2). Data indicate that the pioneer round of translation promotes the removal of the EJCs and the replacement of PABPN1 by PABPCl. EJC removal is mediated by elongating ribosomes, presumably in association with PYM (not shown), which explains why a PTC situated less than ~30–35 nucleotides upstream of or downstream from the 3′-most EJC generally does not trigger NMD: There is no surviving EJC downstream from the PTC (see Fig. 3). The mechanism by which translation promotes the replacement of PABPN1 by PABPC1 is less certain. (N) nucleus, (C) cytoplasm.
