engleski

RNA – a novel substrate of bacterial ADP- ribosyltransferases

ADP-ribosylation is an evolutionarily conserved reversible post-translational modification utilized from bacteria to humans. Streptomyces coelicolor is a bacterial model with very lively ADP-ribosylation metabolism. Based on primary sequences of known ADP-ribosyltransferases and hydrolases, more than a dozen potential enzymes were identified. Streptomyces proteins mediating ADP-ribosylation act to control important pathways such as morphological differentiation and antibiotic production. Using in vitro activity assays we identified RNA as a novel target of reversible mono-ADP- ribosylation. We demonstrated that the S. coelicolor protein SCO3953 can ADP- ribosylate phosphorylated ends of RNA. We also show that E. coli KptA, yeast Tpt1 and human TRPT1 (PARP18) homologues possess activities comparable to the Streptomyces protein. This modification is reversible and can be removed by several ADP- ribosylhydrolases. Our data suggest that RNA ADP- ribosylation may represent a widespread and physiologically relevant form of reversible ADP- ribosylation signalling. Further efforts will be put into defining the specificity to certain RNA molecules as well as the physiological significance of this pathway.

ADP-ribosylation, macrodomain, nucleic acid ADP-ribosylation

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