Gene regulation meets redox biochemistry – NAD-capped RNA in pro- and eukaryotes

Andres Jäschke

Heidelberg University,

The absence of capped RNA has long been considered as a hallmark of prokaryotic gene expression. The combination of next-generation sequencing with chemo-enzymatic capture allowed the enrichment and analysis of rare 5’-modified RNA from bacteria. This approach identified covalent cap-like linkage of a specific set of small RNAs to the ubiquitous redox cofactor NAD, and a profound influence of this modification on RNA turnover. The modification revealed an unexpected connection between redox biology and RNA processing. To date, NAD-RNAs have been identified in the bacteria Escherichia coli, Bacillus subtilis, and Staphylococcus aureus, as well as in the eukaryotes Saccharomyces cerevisiae, Arabidopsis thaliana, and Homo sapiens. While mechanistic work has identified pathways of biosynthesis and removal of the NAD cap, its biological roles are still largely enigmatic. I will discuss possible roles of the NAD modification as well as broader implications for structurally related cofactors and metabolites which may also be linked to RNAs, leading to a new epitranscriptomic layer of information encoded in the chemical structure of the attached cofactors. I will further discuss our efforts to unravel the structure and function of bacterial capping and decapping enzymes, and to understand the influence of cap structures on bacterial and eukaryotic physiology. I will present recent progress on NAD capping and decapping in other bacteria.

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