Pietrow Paulina, Ferenc-Mrozek Aleksandra, Piecyk Karolina, Bojarska Elzbieta, Darzynkiewicz Edward, Jankowska-Anyszka Marzena
Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland.
Division of Biophysics, Institute of Experimental Physics, Faculty of Physics and Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.
ACS Omega. 2019 Oct 9;4(17):17576-17580. doi: 10.1021/acsomega.9b02715. eCollection 2019 Oct 22.
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), (CeDcpS), and (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.
mRNA降解是基因表达调控的关键机制。在3'→5'衰变途径中，mRNA被外切体复合物降解，产生的帽二核苷酸或短帽寡核苷酸主要被脱帽清除酶（DcpS）——组氨酸三联体家族的一员水解。不同物种的DcpS脱帽机制相似；然而，它们各自的底物特异性不同。在本文中，我们描述了探索人源（hDcps）、秀丽隐杆线虫（CeDcpS）和非洲爪蟾（AsDcpS）的DcpS对在7-甲基鸟苷N2位置修饰的二核苷酸帽类似物的活性的实验。测试了各种烷基取代基，碳链长度超过三个碳的帽类似物不能被hDcpS和CeDcpS水解。修饰后的帽类似物对hDcpS和CeDcpS的抗性可能与其与酶的较弱结合有关。
