title: Applications of Phosphate Modification and Labeling to Study (m)RNA Caps.
abstract: The cap is a natural modification present at the 5' ends of eukaryotic messenger RNA (mRNA), which because of its unique structural features, mediates essential biological functions during the process of gene expression. The core structural feature of the mRNA cap is an N7-methylguanosine moiety linked by a 5'-5' triphosphate chain to the first transcribed nucleotide. Interestingly, other RNA 5' end modifications structurally and functionally resembling the m7G cap have been discovered in different RNA types and in different organisms. All these structures contain the 'inverted' 5'-5' oligophosphate bridge, which is necessary for interaction with specific proteins and also serves as a cleavage site for phosphohydrolases regulating RNA turnover. Therefore, cap analogs containing oligophosphate chain modifications or carrying spectroscopic labels attached to phosphate moieties serve as attractive molecular tools for studies on RNA metabolism and modification of natural RNA properties. Here, we review chemical, enzymatic, and chemoenzymatic approaches that enable preparation of modified cap structures and RNAs carrying such structures, with emphasis on phosphate-modified mRNA cap analogs and their potential applications.
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki i Wigury 93, 02-089, Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Warminski
authors.affiliation: Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland.
authors.forename: Pawel J
authors.initials: PJ
authors.lastname: Sikorski
authors.affiliation: Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Zwirki i Wigury 93, 02-089, Warsaw, Poland. asia@biogeo.uw.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kowalska
authors.affiliation: Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland. jacekj@biogeo.uw.edu.pl.
authors.forename: Jacek
authors.identifier: http://orcid.org/0000-0001-7633-788X
authors.initials: J
authors.lastname: Jemielity
mesh_terms: D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010710:Phosphates; D012333:RNA, Messenger
keywords: 7-methylguanosine; Cap analog; Capping; Molecular probe; Nucleotide; RNA labeling