Interaction of human decapping scavenger with 5′ mRNA cap analogues: structural requirements for catalytic activity

The cap structure is a specific feature of the 5 � end of mRNA which plays an important role in the post-transcriptional control in gene expression. A major step of gene regulation occurs at the level of mRNA turnover. Degradation of most eukaryotic mRNAs entails the removal of the cap structure in the various pathways. A human scavenger decapping enzyme (hDcpS) catalyses the cleavage of the residual cap structure m 7 GpppN and/or short oligonucleotides after the 3 � → 5 � exosom mediated digestion. In this paper we report a fluorescence study of association process of hDcpS with m 7 GMP, m 7 GDP and selected dinucleotide cap analogues resistant to enzymatic hydrolysis. The calculated values of association constants (Kas) and corresponding Gibbs free energies (� G ◦ ) depend on the type of substituents and their positions in the cap molecule, indicating which structural modifications are crucial for the catalysis.