Messenger RNA 5’ NAD+ Capping is a Dynamic Regulatory Epitranscriptome Mark that is Required for Proper Response to Abscisic Acid in Arabidopsis

Abstract

Although eukaryotic messenger RNAs (mRNAs) normally possess a 5’ end N7-methyl guanosine (m7G) cap, a non-canonical 5’ nicotinamide adenine dinucleotide (NAD+) cap can tag certain transcripts for degradation mediated by the NAD+ decapping enzyme DXO1. Despite its importance as a post-transcriptional regulator, whether NAD+ capping dynamically responds to specific stimuli to regulate eukaryotic transcriptomes remains unknown. Here, we reveal that NAD+ capping is a widespread and tissue-specific mechanism to regulate mRNA stability. In the absence of DXO1 function, NAD+ capped transcripts are instead degraded via a RNA-DEPENDENT RNA POLYMERASE 6-mediated small RNA biogenesis mechanism to permit recycling of the trapped NAD+ molecules. Remarkably, the NAD+ capped transcriptome is significantly remodeled in response to the essential plant hormone abscisic acid in a mechanism that is primarily independent of DXO1. Overall, our findings reveal a previously uncharacterized and essential role of NAD+ capping in dynamically regulating transcript stability during specific physiological responses.