Role of RNF20/40-mediated eEF1B$\delta$L monoubiquitylation in heat shock-responsive transcription

Abstract

RNF20/40, an E3 ubiquitin ligase that mediates histone H2B lysine 120 monoubiquitylation, has important roles in diverse biological events. However, it is uncertain whether these RNF20/40-mediated events are through only H2B ubiquitylation. Here, using biochemically defined systems with purified factors and cell-based analyses, I elucidated that RNF20/40 monoubiquitylates lysine 381 of eEF1B$\delta$L, a heat shock-responsive transcription factor. In particular, this study provides mechanistic insight into the role of monoubiquiylation of eEF1B$\delta$L, which increases eEF1B$\delta$L accumulation and enhances recruitment of p-TEFb to the promoter regions of target genes, resulting in the activation of heat shock-responsive gene expression. Furthermore, I also demonstrate that cooperative interactions among eEF1B$\delta$L, RNF20/40, and HSF1 synergistically promote expression of heat shock-responsive genes. In addition to identifying eEF1B$\delta$L as an ubiquitylation target of RNF20/40 and elucidating its function in response to thermal stress, this study reveals a molecular mechanism for the cooperative function of distinct heat shock-responsive transcription factors and provides novel evidence of a non-proteolytic function of ubiquitylation through RNF20/40-mediated non-histone protein monoubiquitylation.