Translational fidelity screens in mammalian cells reveal eIF3 and eIF4G2 as regulators of start codon selectivity.

ABSTRACT: The translation initiation machinery and the ribosome orchestrate a highly dynamic scanning process to distinguish proper start codons from surrounding nucleotide sequences. Here, we performed genome-wide CRISPRi screens in human K562 cells to systematically identify modulators of the frequency of translation initiation at near-cognate start codons. We observed that depletion of any eIF3 core subunit promoted near-cognate start codon usage, though sensitivity thresholds of each subunit to sgRNA-mediated depletion varied considerably. Double sgRNA depletion experiments suggested that enhanced near-cognate usage in eIF3D depleted cells required canonical eIF4E cap-binding and was not driven by eIF2A or eIF2D-dependent leucine tRNA initiation. We further characterized the effects of eIF3D dep

SUBMITTER: She R 

PROVIDER: S-EPMC10325891 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature