Analýza vzájemných interakcí komponent lidského multifaktoriálního komplexu v iniciaci translace

Prilepskaja, Terezie

A key task of translation initiation is to select a proper start codon. The start codon defines not only the position from which the protein translation is initiated but also the reading frame in which the protein sequence is decoded. The accuracy of start codon recognition is controlled by number of initiation factors (eIFs) and their mutual interactions. One of them, the largest, is called eukaryotic initiation factor 3 (eIF3). The exact mechanism by which eIF3 affects the accuracy of start codon recognition is not understood. Here, using CryoEM, formaldehyde gradient cross- linking and various biochemical methods, we elucidated contributions of individual human eIF3 subunits to this intricate process. In particular, my work and the work of our collaborators revealed that eIF3d promotes loading of eIF3 to the ribosome at the onset of initiation and that the minimalistic eIF3 subcomplex (YLC - for Yeast Like Complex) still preserves basic eIF3 functions, like formation of the 43S pre- initiation complex (PIC) and mRNA recruitment. Another study then implicated human eIF3c is fine-tuning the fidelity of start codon recognition, as downregulation of eIF3c causes a codon- specific decrease in start codon recognition fidelity and an increase in the eIF5 abundance; eIF5 is together with eIFs 1, 1A and...

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