RNA as a target for ADP-ribosylation

RNA as a target for ADP-ribosylation

The human genome encodes several poly(ADP-ribose) polymerases (PARPs), which are enzymes involved in ADP-ribosylation, a reversible chemical modification, of macromolecules such as proteins and DNA. ADP-ribosylation occurs in both prokaryotes and eukaryotes and is linked to vital cellular processes namely stress responses, DNA repair, host-virus interactions, etc. This modification is mostly associated with proteins and to some extent, DNA. It was recently proposed that RNA molecules could also be cellular targets of ADP-ribosylation.

Deeksha Munnur and colleagues from Ivan Ahel’s lab, have now shown that ADP-ribosylation of RNA molecules indeed happens and is a more common phenomenon than previously believed. They found that ADP-ribosylation occurs at the terminal phosphate of RNA forming a non-canonical RNA cap and can be regulated by both PARP-like proteins from bacteria and by some human PARPs. Furthermore, they provide the first evidence that ADP-ribosylation of RNA is a reversible process that can be controlled by ADP-ribosylhydrolases from human as well as VEEV and SARS viruses. This study shines a light on a new regulatory mechanism of RNA molecules with potential therapeutic relevance.

Iqbal Dulloo

Munnur D, Bartlett E, Mikolčević P, Kirby IT, Matthias Rack JG, Mikoč A, Cohen MS, Ahel I.

Nucleic Acids Res. 47(11): 5658-5669