Nature Communications · 2023 · 16 citations · 39 references
Life SciencesGeneticsMolecular BiologyEpigeneticsGene ExpressionGenomicsRna InterferenceRna StructureRna-binding ProteinsTelomere BiologyHuman African TrypanosomiasisMonoallelic ExpressionMonoallelic Gene ExpressionRna Recognition MotifsRna-binding Domain StructureRna-binding MotifRna-protein BindingTelomere-associated Proteins
Abstract Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein Tb RAP1 binds dsDNA through its 737 RKRRR 741 patch to silence VSGs globally. How Tb RAP1 permits expression of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in Tb RAP1, which is unprecedented for RAP1 homologs. Assisted by the 737 RKRRR 741 patch, Tb RAP1 RRM recognizes consensus sequences of VSG 3’UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs . The competition between Tb RAP1’s RNA and dsDNA binding activities suggests a VSG monoallelic expression mechanism in which the active VSG ’s abundant RNA antagonizes Tb RAP1’s silencing effect, thereby sustaining its full-level expression.
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Highly accurate protein structure prediction with AlphaFold
John Jumper, Alexander Pritzel, Tim Green et al. · Nature · 2021 · 45.2K citations · Full text