During lymphocyte development, a diverse repertoire of lymphocyte antigen receptors is produced to battle against pathogens, which is the basis of adaptive immunity. The diversity of the lymphocyte antigen receptors arises primarily from recombination-activated gene (RAG) protein-mediated V(D)J rearrangement in early lymphocytes. Furthermore, transcription factors (TFs), such as early B cell factor 1 (EBF1), paired box gene 5 (PAX5), and proto-oncogene myelocytomatosis oncogene (MYC), play critical roles in regulating recombination and maintaining normal B cell development. Therefore, the aberrant expression of these TFs may lead to hematologic neoplasms.

As one member of the heterogeneous ribonucleoprotein (hnRNP) family, scaffold attachment factor A (SAF‑A) or hnRNP U, is an abundant nuclear protein. With RNA and DNA binding activities, SAF‑A has multiple functions. The present review focused on the biological structure and different roles of SAF‑A and SAF‑A‑related diseases. It was found that SAF‑A maintains the higher‑order chromatin organization via RNA and DNA, and regulates transcription at the initiation and elongation stages. In addition to regulating pre‑mRNA splicing, mRNA transportation and stabilization, SAF‑A participates in double‑strand breaks and mitosis repair. Therefore, the aberrant expression and mutation of SAF‑A results in tumors and impaired neurodevelopment. Moreover, SAF‑A may play a role in the anti‑virus system. In conclusion, due to its essential biological functions, SAF‑A may be a valuable clinical prediction factor or therapeutic target. Since the role of SAF‑A in tumors and viral infections may be controversial, more animal experiments and clinical assays are needed.

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.