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

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Nucleic acid binding proteins regulate gene expression through various mechanisms.
• Traditionally classified as DNA or RNA binders, many proteins exhibit dual binding capabilities.
• High mobility group box (HMGB) proteins are recognized for DNA binding and transcriptional roles.

Purpose of the Study:

• To comprehensively review evidence supporting HMGB proteins as dual DNA and RNA binding proteins.
• To highlight the functional implications of HMGB-RNA interactions in gene regulation.
• To explore the role of HMGB-RNA interactions in human diseases.

Main Methods:

• In vitro and in vivo biochemical assays to detect direct HMGB-RNA interactions.
• Cellular localization studies, particularly in RNA processing granules.
• Analysis of protein interactors and their enrichment in RNA metabolism pathways.
• Investigation of HMGB-RNA interactions in cell-based systems to assess functional impacts.

Main Results:

• HMGB proteins demonstrate direct binding to RNA in vitro and in vivo.
• HMGB proteins localize to RNA-protein (RNP) granules involved in RNA metabolism.
• HMGB-RNA interactions influence protein-protein interactions, splicing, and protein localization.
• Misregulation of HMGB-RNA interactions is implicated in human diseases.

Conclusions:

• The HMGB protein family exhibits dual DNA and RNA binding capabilities.
• RNA binding is an essential, often overlooked, aspect of HMGB protein biology.
• Understanding HMGB-RNA interactions is critical for comprehending gene regulation and disease pathogenesis.