Autoregulation of YB-1 Synthesis in Cells

Abstract The Y-box binding protein 1 (YB-1) plays a crucial role in regulating essential cell functions, including transcription, translation, and DNA repair, through its interactions with nucleic acids and multiple protein partners. The multifunctionality of YB-1 makes the control of its levels critical for cellular homeostasis and adaptation to stress. The synthesis of YB-1 is regulated by gene transcription, protein stability (mediated by long non-coding RNAs), and translation of its mRNA. Autoregulation of YB-1 mRNA translation remains the topic of ongoing debate. Some earlier in vitro studies suggested a role of the 5′ untranslated region (UTR) in inhibiting protein synthesis, while others demonstrated the importance of YB-1 binding to the 3′ UTR for reducing translation. This disagreement has been further complicated by the absence of evidence for these mechanisms in living cells. Here, we provide the first direct evidence that YB-1 represses its synthesis in cultured human cells. Using metabolic protein labeling and immunopre