In non-polarized cells, the pioneer round of translation, i.e., the translation of newly made CBC-bound mRNAs, and 3UTR EJC-mediated NMD, can take place either on the cytoplasmic side of the nuclear envelope (shown) or after disassociating with the nuclear envelop (no shown). Generally, those 3UTR EJC-mediated NMD targets that escape decay are remodeled to contain eIF4E at their 5 cap, lose any remaining EJCs, and become immune to further NMD (not shown), unless they continue to undergo NMD mediated by a long and/or structured 3UTR. While the decay of newly made CBC-bound mRNAs whose NMD is triggered by a long and/or structured 3UTR can also occur on the cytoplasmic side of the nuclear envelope, once remodeled to eIF4E-bound mRNAs, they continue to undergo NMD, presumably in the cytosol (not shown). Note that while NMD targets are generally bound by FMRP, the FMRP-mediated block in translation is incomplete since FMRP binding is not 100% efficient. FMRP is not shown. Red pacman, NMD decay machinery; CBC, CBP80 CBP20 at the 5 m 7 G cap of newly made mRNAs; green balls, 80S ribosome with nascent peptide; STOP, translation termination codon; EJC, exon-junction complex.
