The DNA binding high mobility group box protein family functionally binds RNA

Nucleic acid binding proteins regulate transcription, splicing, RNA stability, RNA localization, and translation, together tailoring gene expression in response to stimuli. Upon discovery, these proteins are typically classified as either DNA or RNA binding as defined by their in vivo functions; however, recent evidence suggests dual DNA and RNA binding by many of these proteins. High mobility group box (HMGB) proteins have a DNA binding HMGB domain, act as transcription factors and chromatin remodeling proteins, and are increasingly understood to interact with RNA as means to regulate gene expression. Herein, multiple layers of evidence that the HMGB family are dual DNA and RNA binding proteins is comprehensively reviewed. For example, HMGB proteins directly interact with RNA in vitro and in vivo, are localized to RNP granules involved in RNA processing, and their protein interactors are enriched in RNA binding proteins involved in RNA metabolism. Importantly, in cell-based systems, HMGB-RNA interactions facilitate protein-protein interactions, impact splicing outcomes, and modify HMGB protein genomic or cellular localization. Misregulation of these HMGB-RNA interactions are also likely involved in human disease. This review brings to light that as a family, HMGB proteins are likely to bind RNA which is essential to HMGB protein biology.This article is categorized under:RNA Interactions with Proteins and Other Molecules > Protein-RNA RecognitionRNA Interactions with Proteins and Other Molecules > RNA-Protein ComplexesRNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications

Automated summary

Nucleic acid binding proteins, specifically the high mobility group box (HMGB) proteins, have dual DNA and RNA binding abilities, allowing them to regulate gene expression. Through direct interaction with RNA, localization in RNA processing granules, and interactions with RNA binding proteins, HMGB proteins play crucial roles in protein-protein interactions, splicing outcomes, and genomic/cellular localization. Misregulation of HMGB-RNA interactions may also contribute to human diseases.