# Mechanisms and functions of RNA NAD+ capping and decapping

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2021 · $199,758

## Abstract

PROJECT SUMMARY
The RNA m7G cap has been recognized as a capstone in RNA metabolism in eukaryotes, thanks to decades
of research that uncovered the mechanisms underlying its deposition, removal, and impacts on gene
expression. However, recent discoveries showing that the m7G cap is not the only RNA cap indicate that our
knowledge of RNA metabolism is far from complete. Nicotinamide adenine diphosphate (NAD+) has recently
emerged as an RNA cap in bacteria, yeast, and humans, and our preliminary studies show that this cap is
widespread in the model plant Arabidopsis; thus, NAD+ maybe a universal RNA cap in life. Existing evidence
points to a dynamic nature of this RNA modification, as enzymes that deposit and remove the NAD+ cap have
been identified in bacteria, humans, and Arabidopsis. The potentially dynamic nature of this RNA modification
points to its as yet unknown regulatory functions in gene expression and biological processes. As NAD+ serves
critical functions in cellular redox and energy homeostasis, it is possible that NAD+ capping/decapping in RNA
is both regulated by and impacts cellular redox and metabolic homeostasis. Despite its potential importance,
our knowledge of the NAD+ cap is at most rudimentary.
 The project seeks to understand the biology of the RNA NAD+ cap using the Arabidopsis model. Based
on preliminary studies that documented the existence of NAD+-capped RNAs, implicated their translational
status and revealed potential decapping enzymes, the project interrogates how the NAD+ cap is deposited and
removed, how the NAD+ cap impacts gene expression, and what biological processes are regulated by RNA
NAD+-capping/decapping. The sophisticated molecular and genetic resources in the Arabidopsis model not
only allow for the understanding of this universal RNA modification in one domain of life, but also offer
advantages of studying this RNA modification in an intact, multicellular life with relative ease. Findings on the
RNA NAD+ cap from this project may have far-reaching impacts in agriculture and medicine.

## Key facts

- **NIH application ID:** 10385495
- **Project number:** 3R01GM061146-21S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Xuemei Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $199,758
- **Award type:** 3
- **Project period:** 2000-05-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385495

## Citation

> US National Institutes of Health, RePORTER application 10385495, Mechanisms and functions of RNA NAD+ capping and decapping (3R01GM061146-21S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10385495. Licensed CC0.

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