It is therefore also not clear, whether this mRNA increase resulted from an inhibition of NMD or from a Clofibric Acid general mRNA stabilization. Most interestingly, tethering of the eIF4G core domain alone, encompassing the RRM and the MIF4G domain, also efficiently suppressed NMD. Since the eIF4G core domain lacks both the PABPC1 and the eIF4E binding sites, this effect cannot be attributed to formation of a ����closed loop���� configuration and therefore provides evidence for an independent second mechanism of NMD suppression. We hypothesized that eIF4G in the vicinity of a PTC might inhibit NMD by promoting re-initiation of translation further downstream on the reporter mRNA. However, our attempt to detect polypeptides originating from such putative re-initiation events on the minim reporter transcript failed. Thus, although we have no evidence for re-initiation being involved, we cannot either rule it out based on these negative results. Finding that the eIF4G core domain was Catharanthine sulfate capable of antagonizing NMD suggested that the same might be true for CTIF, because CTIF contains a highly homologous MIF4G domain and was reported to functionally replace eIF4G during translation initiation of CBC-associated mRNAs. In the tethering assay, however, CTIF was not capable of antagonizing NMD despite of its robust expression. The specific motifs in the eIF4G core domain responsible for the observed NMD suppression remain therefore to be identified. A well-characterized interactor of the eIF4G core domain is the eIF3 complex. Besides its function in translation initiation, eIF3 was shown to be involved in disassembling the post termination ribosome and recycling of the ribosomal subunits in a reconstituted in vitro system. Moreover, a role for eIF3 in translation termination has recently been documented in yeast cells. Specifically, the pulldown assays of Beznoskova and colleagues provided evidence for an association of eIF3 with release factors Sup45p and Sup35p as well as with the ribosome recycling factor Rli1.Furthermore, there is also evidence for a link between eIF3 and NMD, but collectively the data does not provide an easily interpretable picture: subunit a was shown to interact with phosphorylated UPF1, subunit e was identified as an essential NMD factor associated with UPF2 and the CTIF interacting subunit g inhibits NMD when down-regulated, whereas subunits f and h are required to prevent NMD of b-globin reporter transcripts with AUG proximal PTCs.