Human tumor suppressor PDCD4 directly interacts with ribosomes to repress translation
Xianwen Ye, Zixuan Huang, Yi Li, Mengjiao Wang, Wanyu Meng, Maojian Miao, Jingdong Cheng
Abstract
Protein translation regulation is a crucial and tightly controlled regulatory process that contributes to phenotypic diversity among cells with identical or similar genotypes. Across all the steps of translation, initiation is the most energy- and time-intensive stage. In eukaryotes, this process starts with the assembly of the 43S preinitiation complex (PIC), comprising 40S ribosome, eIF1, eIF1A, the eIF3 complex (eIF3A-M), eIF5, and the ternary complex (TC, consisting of eIF2α/β/γ, tRNA iMet , and GTP). After 43S PIC assembly, the eIF4F complex (consisting of the DEAD box helicase eIF4A, eIF4B, eIF4E, and eIF4G) is recruited, along with the mRNA, to form the 48S initiation complex (IC). Following the recognition of the first cognate AUG start codon by the 48S IC, the 60S ribosome joins to initiate translation elongation. This process requires a coordination of multiple complexes and factors for rigorous regulation of protein translation. 1 Importantly, cells employ various mechanisms to inhibit translation initiation in response to environmental stress conditions, yet the detailed molecular mechanisms have not been fully elucidated.