LAUSR

mRNA degradation is a key mechanism of gene expression regulation. In the 3′ → 5′ decay pathway, mRNA is degraded by the exosome complex and the resulting cap dinucleotide or short-capped oligonucleotide is hydrolyzed mainly by a decapping scavenger enzyme (DcpS)—a member of the histidine triad family. The decapping mechanism is similar for DcpS from different species; however, their respective substrate specificities differ. In this paper, we describe experiments exploring DcpS activity from human (hDcps), Caenorhabditis elegans (CeDcpS), and Ascaris suum (AsDcpS) toward dinucleotide cap analogues modified at the N2 position of 7-methylguanosine. Various alkyl substituents were tested, and cap analogues with a longer than three-carbon chain were nonhydrolyzable by hDcpS and CeDcpS. Resistance of the modified cap analogues to hDcpS and CeDcpS may be associated with their weaker binding with enzymes.