Seminarium Zakładu Biofizyki

Despite the structure of human DcpS (Decapping Scavenger) protein has been resolved, little is known about the mechanism of mRNA cap (5’ end of mRNA) hydrolysis by the enzymes of the DcpS family. Degradation of the cap by DcpS is a critical step in the regulation of mRNA turnover and is thought to be very important for preventing the cap inhibition of other cap binding proteins, such as eIF4E and CBC. Recently, DcpS was shown to play also a role in RNA splicing. Moreover, it has been recognized as a novel therapeutic target for spinal muscular atrophy (SMA). The biological functions of DcpS make it an interesting object for biophysical and biochemical investigations. On the seminar it will be presented quantitative analyses on the ability of DcpS from C. elegans to act on various cap analogs using fluorescence titration, enzyme kinetics and HPLC analysis. A series of modified dinucleotide cap analogs studied enable to define several key DcpS structural requirements for substrate specificity and promise to further understanding the cap-specific regulation of the gene expression on the molecular level. The all-embracing knowledge of mRNA cap-DcpS interactions is indispensable to find selective inhibitors of processes in which nucleotide-binding proteins are involved.