A novel mRNA modification may impact the human genetic code

2018

Challenge

There are more than one hundred ways an RNA molecule can be chemically modified after it is synthesized. The functions of many of these modifications, collectively referred to as the epitranscriptome, are largely unknown.

Advance

IRP senior investigator Shalini Oberdoerffer, Ph.D., identified a novel modification in human messenger RNA (mRNA) that dramatically impacts the activity of genes by promoting the production of protein from RNA. Intriguingly, NAT10, the enzyme responsible for the mRNA modification, had been previously implicated in cancer and aging.

Impact

This is one of the first examples of a unique chemical modification to mRNA that increases the amount of protein produced by a gene. With a deep understanding of the epitranscriptome, it may one day be possible to manipulate it in order to adjust the levels of disease-associated proteins.

Publications

Arango D, Sturgill D, Alhusaini N, Dillman AA, Sweet TJ, Hanson G, Hosogane M, Sinclair WR, Nanan KK, Mandler MD, Fox SD, Zengeya TT, Andresson T, Meier JL, Coller J, Oberdoerffer S. (2018). Acetylation of cytidine in mRNA promotes translation efficiency. Cell. 175(7):1872-1886.