ИСТИНА

Glycyl-tRNA synthetase serves as unusual IRES trans acting factor for type I picornavirus IRESes, as its recruitment to tRNA anticodon-like element located in domain V is necessary for efficient translation initiation. Here we show that in RRL, which is deficient on GARS, the translation driven by PV and HRV IRESs can be stimulated by addition of either p100 fragment of eIF4G, or by smaller 4G middle domain. However, for RRL supplemented with GARS, the effects of p100 and 4G MD on translation becomes opposing: whereas p100 still stimulates translation, 4G MD inhibits it. Intriguingly, when putative upstream initiation codon AUG586 in PV IRES is mutated, the stimulatory effect of GARS on translation is reduced and 4G MD effect is reversed from inhibition to stimulation. Consequently, when repoter gene is translated directly from AUG586, the effect of GARS on translation becomes more prominent and 4G MD starts to act as inhibitor. We propose that GARS stimulates eIF4G binding to IRESs of type I and regulates ribosomal entry to putative upstream AUG from which it is redirected to correct initiation codon.