Applications of Phosphate Modification and Labeling to Study (m) RNA Caps

作者:Warminski Marcin; Sikorski Pawel J; Kowalska Joanna*; Jemielity Jacek*
来源:Topics in Current Chemistry, 2017, 375(1): 16.
DOI:10.1007/s41061-017-0106-y

摘要

The cap is a natural modification present at the 50 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 50-50 triphosphate chain to the first transcribed nucleotide. Interestingly, other RNA 50 end modifications structurally and functionally resembling the m(7)G cap have been discovered in different RNA types and in different organisms. All these structures contain the 'inverted' 50-50 oligophosphate bridge, which is necessary for interaction with specific proteins and also serves as a cleavage site for phospho-hydrolases 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.

  • 出版日期2017-2