Messenger RNA 5' NAD+ Capping Is a Dynamic Regulatory Epitranscriptome Mark That Is Required for Proper Response to Abscisic Acid in Arabidopsis

Dev Cell. 2021 Jan 11;56(1):125-140.e6. doi: 10.1016/j.devcel.2020.11.009. Epub 2020 Dec 7.

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 this importance, whether NAD+ capping dynamically responds to specific stimuli to regulate eukaryotic transcriptomes remains unknown. Here, we reveal a link between NAD+ capping and tissue- and hormone response-specific mRNA stability. In the absence of DXO1 function, transcripts displaying a high proportion of NAD+ capping are instead processed into RNA-dependent RNA polymerase 6-dependent small RNAs, resulting in their continued turnover likely to free the NAD+ molecules. Additionally, 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.

Keywords: ABA; NAD capping; RNA degradation; RNA modification; RNA stability; abscisic acid; epitranscriptome; post-transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abscisic Acid / pharmacology*
  • Arabidopsis / enzymology
  • Arabidopsis / genetics
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • Chloroplast Proteins / genetics
  • Chloroplast Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Gene Ontology
  • NAD / metabolism*
  • Plants, Genetically Modified
  • RNA Processing, Post-Transcriptional / genetics*
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Small Untranslated / genetics
  • RNA, Small Untranslated / metabolism*
  • Transcription Factors / genetics
  • Transcriptome / drug effects*
  • Transcriptome / genetics*

Substances

  • Arabidopsis Proteins
  • CONSTANS protein, Arabidopsis
  • Chloroplast Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA, Small Untranslated
  • Transcription Factors
  • NAD
  • Abscisic Acid
  • AT4G17620 protein, Arabidopsis
  • Exoribonucleases