HuB serves as the central hub for connecting HuR-related mRNAs with translation machinery in inflammation.

The mRNAs of inflammatory factors often contain unstable AU-rich elements (AREs) within their 3' untranslated regions (3'UTRs), and HuR is a key ARE-binding protein to recognize such elements. However, the roles of other Hu family member (s) remain unclear. In this study, we show an inflammatory stimulation-induced short-form and cytoplasm-localized HuB (Hel-N2). In cytoplasm, HuB interacts with HuR as well as HuR-associated pro-inflammatory cytokine/chemokine mRNAs and facilitates the recruitment of these mRNAs into the translation machinery. Furthermore, HuB recruits RNA helicase DHX9 to unwind the secondary structures presented in the 5' untranslated regions (5'UTRs) of these mRNAs, thereby promoting their translation. The work has been carried out in human and mouse cell lines and female mice. Our finding not only broadens our understanding about how the Hu family members govern pro-inflammatory gene expression, but also suggests that targeting HuB is a viable strategy to treat inflammation-related diseases.