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

• Published in: Journal of physics. Condensed matter Vol. 19; no. 28; pp. 285217 - 285217 (6)
• Main Authors: Darzynkiewicz, Zbigniew M, Bojarska, Elzbieta, Kowalska, Joanna, Lewdorowicz, Magdalena, Jemielity, Jacek, Kalek, Marcin, Stepinski, Janusz, Davis, Richard E, Darzynkiewicz, Edward
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Bristol IOP Publishing 18.07.2007; Institute of Physics
• Subjects: Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene expression; Molecular and cellular biology; Molecular genetics; Human; 5' terminal-Sequence; Messenger RNA; Cap structure; Interaction; Gene expression; Posttranscriptional modification
• ISSN: 0953-8984; 1361-648X
• DOI: 10.1088/0953-8984/19/28/285217

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 m7GpppN and/or short oligonucleotides after the exosom mediated digestion. In this paper we report a fluorescence study of association process of hDcpS with m7GMP, m7GDP and selected dinucleotide cap analogues resistant to enzymatic hydrolysis. The calculated values of association constants (Kas) and corresponding Gibbs free energies (DeltaG deg ) depend on the type of substituents and their positions in the cap molecule, indicating which structural modifications are crucial for the catalysis.