Decapping Scavenger Enzyme Activity toward N2-Substituted 5' End mRNA Cap Analogues

Paulina Pietrow; Aleksandra Ferenc-Mrozek; Karolina Piecyk; Elzbieta Bojarska; Edward Darzynkiewicz; Marzena Jankowska-Anyszka

doi:10.1021/acsomega.9b02715

Decapping Scavenger Enzyme Activity toward N2-Substituted 5' End mRNA Cap Analogues

ACS Omega. 2019 Oct 9;4(17):17576-17580. doi: 10.1021/acsomega.9b02715. eCollection 2019 Oct 22.

Authors

Paulina Pietrow¹, Aleksandra Ferenc-Mrozek², Karolina Piecyk¹, Elzbieta Bojarska², Edward Darzynkiewicz^{2

2}, Marzena Jankowska-Anyszka¹

Affiliations

¹ Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
² Division of Biophysics, Institute of Experimental Physics, Faculty of Physics and Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.

Abstract

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.