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Molecular principles of translation reinitiation in mammals
Hronová, Vladislava ; Valášek, Leoš (advisor) ; Krásný, Libor (referee) ; Staněk, David (referee)
Translation initiation is a multistep process resulting in the formation of the elongation-competent 80S ribosome at the AUG start codon of the mRNA to be translated into a polypeptide chain. This process is orchestrated by numerous proteins called eukaryotic initiation factors (eIFs), out of which the most multitasking one is the eukaryotic initiation factor 3 (eIF3). The main focus of our laboratory aims at the complex characterization of the multisubunit protein eIF3 and the mechanisms of its contribution to various steps of translation initiation. Besides this, we also study one of the gene-specific translational control mechanisms called reinitiation which was, at least in yeast, also shown to be promoted by eIF3. Here I show that the N-terminal domain (NTD) of the largest subunit of yeast eIF3, a/Tif32, plays an important role not only in anchoring the eIF3 complex to the 40S small ribosomal subunit but it also critically contributes to mRNA recruitment to the 43S preinitiation complexes in vivo. The mRNA stabilization role of the a/Tif32-NTD at the mRNA exit channel of the 40S subunit was further confirmed in our following study by biophysical experiments. There, using in vivo approaches, we also demonstrated that mRNAs with longer 5'UTRs are more dependent on the stabilization role of the...

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