hnRNPs in immunity: from nucleic acid sensing to lymphocyte fate determination

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a family of RNA-binding proteins long recognized for their roles in pre-mRNA processing. However, accumulating evidence has established hnRNPs as central and versatile regulators of immunity. In innate immunity, some hnRNP family members recognize nucleic acids and metabolites to either promote or constrain inflammatory gene expression in a context-dependent manner. In adaptive immunity, they play essential roles in B cell activation and germinal center (GC) responses, as well as T cell activation, survival, and differentiation, primarily through the precise regulation of alternative splicing (AS). Here, we review the functions of hnRNPs (with a focus on A1, A2B1, I, K, L, M, and U) across innate and adaptive immunity, and discuss critical unresolved questions, including the often-overlooked axis of species-specific regulation.