RNA ADP-ribosylation

A few years ago, work was published which showed that under certain conditions, some PARPs can modify RNA with ADP-ribose in vitro. Many questions were left unanswered: can all PARPs do this? Do they modify RNA in cells? What is the function of RNA ADP-ribosylation, how does it influence the modified molecules?

We were intrigued by these questions and started looking for answers. In our newest publication, titled “ADP-ribosylation of RNA in mammalian cells is mediated by TRPT1 and multiple PARPs”, we show that RNA can be ADP-ribosylated in human cells. We found that the modification is rapidly reversed by hydrolases and can be detected best in hydrolase knockdown cells. Diverse stimuli lead to enhanced modification.

We also tested how the modified molecules are influenced in vitro. The modified RNA is, perhaps not surprisingly considering the lack of a conventional cap, not translated and is protected from XRN1-mediated degradation. Intriguingly, the ADP-ribosylated RNA can be ligated by the bacterial T4 RNA ligase 1 in an ATP-independent manner. This ligation leads to the incorporation of a basic site into the ligation product.

This work shows that ADP-ribosylation of RNA occurs in human cells, and that at least in vitro it has functional consequences for the modified RNA. Future work is required to study which PARP modifies which RNAs in response to which stimuli, as well as to further investigate the consequence of modification for individual RNAs.

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