From Mystery to Mechanism: The role of Base J in Transcription Termination and Gene Regulation in Trypanosomatids and other Kinetoplastids

The modified nucleotide β-D-glucopyranosyloxymethyluracil (Base J) is found uniquely in kinetoplastids. Accumulating evidence has linked J to gene expression regulation, though its precise mechanistic role has remained elusive. Recent studies suggest J recruits chromatin restructuring and transcription termination complexes to DNA via a novel J-Binding Protein (JBP3), revealing diverse mechanism of J function. This review provides a comprehensive summary of Base J, exploring its biological roles and outlook as a parasite-specific therapeutic target. The necessity of functional J studies in species beyond Trypanosoma brucei will also be addressed, essential to uncover J functional divergence amongst kinetoplastids.