Phosphate Labeling and Sensing in Chemical Biology

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

by Marcin Warminski, Pawel J. Sikorski, Joanna Kowalska, Jacek Jemielity

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.

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Henning Jessen © SpringerHenning Jessen

Henning Jessen did his PhD in 2008 at the University of Hamburg developing nucleotide prodrugs. He then moved for a postdoctoral stay to the EPFL, Switzerland, and worked on the total synthesis of natural products that promote neurite outgrowth. He started his independent career at the University of Zürich, Switzerland in 2011. In 2015 he was promoted to full professor at the University of Freiburg, Germany. Research in his group is focused on the development of novel phosphorylation methods and their application in the synthesis of challenging targets. Among these are the inositol pyrophosphates, inositol polyphosphates, densely phosphorylated nucleotides, nucleoside diphosphate sugars, and inorganic polyphosphate. Moreover, chemical biology tools to better understand phosphate homeostasis in living cells are being developed in his labs in Freiburg. This line of research is backed up using novel analytical methods to study highly charged metabolites and assign their chemical structure. His research is funded by the Swiss National Science Foundation (SNF), the German Science Foundation (DFG), the Volkswagen Foundation, the Carl-Zeiss Foundation, and the Human Frontier Science Program Organisation (HFSPO).



Institute of Organic Chemistry

Albert-Ludwigs-University of Freiburg

Freiburg im Breisgau

Baden-Württemberg, Germany