Structural basis for non-AUG translation regulation by 5MPs.

ABSTRACT: The cellular proteome is regulated by translation initiation on AUG or non-canonical (non-AUG) start codons^1-3. Non-AUG initiation remodels proteome during stress and is implicated in cancer and other diseases^4-6. The eIF5-mimic proteins (5MPs) restrict non-AUG start codon usage and thereby reprogram proteoform expression from mRNAs with alternative start sites, such as the oncogenic c-Myc^7-10. The mechanism by which 5MPs induce such translational reprogramming remains unknown. Here, using in extracto cryo-electron microscopy (cryo-EM) and biochemical assays, we report that translational repression by 5MP strongly depends on the sequence context near the AUG or non-AUG codons. Cryo-EM structures of 5MP-bound 48S pre-initiation complexes (PICs) from n

SUBMITTER: Zottig X 

PROVIDER: S-EPMC12776414 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature