The mechanism of RNA 5′ capping with NAD+, NADH and desphospho-CoA

Ribonucleic acid (RNA) is central to gene expression. RNA stabilty is determined largely by the chemical nature of the RNA 5' end. A research team including Richard H. Ebright and Jeehiun Katherine Lee in the Department of Chemistry and Chemical Biology at Rutgers and Bryce Nickels in the Department of Genetics at Rutgers have demonstrated that each of three coenzymes--NAD+, NADH, and dpCoA--can serve as a "noncanonical initiating nucleotide" (NCIN) for transcription initiation by bacterial and eukaryotic RNA polymerases, resulting in incorporation of the NCIN at the RNA 5' end as an NCIN "cap." The researchers also identified DNA sequences that influence the efficiency of NCIN capping, demonstrated that NCIN capping occurs in vivo, demonstrated that NCIB capping has functional consequences in vivo, and determined crystal structures of transcription complexes engaged in NCIN capping. The research was published in Nature and can be found, along with accompanying commentary, at http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18622.html and http://www.nature.com/nature/journal/vaop/ncurrent/full/nature18908.html

 

The figure shows crystal structures of transcription initiation complexes containing uncapped and NCIN-capped initial RNA products (uncapped RNA in panel A; NAD+-capped RNA in panel B)

Publication: 

 

Nature (2016)

Doi:10.1038/nature18622

Published online: July 6, 2016

Year of Research Highlight: 
2016