# Ribosomal Skipping Under Oxidative Stress in SLE

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2020 · $352,660

## Abstract

SLE is a chronic autoimmune syndrome that can involve a variety of organ systems and frequently affects young
individuals. It has been suggested that uncontrolled oxidative stress in the cells of SLE patients contributes to
functional oxidative modifications of many proteins, lipids, and DNA, thereby triggering autoimmunity. However,
what role RNA oxidation plays in the regulation of translation and development of autoimmune diseases such as
SLE is not known. Under both normal and oxidative stress conditions, RNA oxidation levels are much higher
than DNA oxidation levels; however, available information on the potential effects of RNA oxidation is scarce
and despite the prevalence and importance of translational regulation, we have a limited view of how oxidative
stress affects translation and protein diversification. A major reason for the paucity of work on RNA oxidation is
the misconception that normal RNA turnover should diminish the effects of oxidized RNA on cell metabolism and
gene expression. However, because oxidation of RNA occurs in just a few minutes, and ribosomal and non-
coding RNAs persist in the cell for days, there is ample opportunity for oxidized RNA to have deleterious and
long-standing effects. Our scientific premise is that MAVS oligomerization-induced accumulation of 5S RNA at
the mitochondria ensures that this RNA is specifically oxidized. We propose that oxidized 5S RNA will promote
ribosomes to perform translation in a skipping mode, which will support translation of proteins that are normally
expressed under cellular stress of viral infection. We propose that, Aim1: In SLE patients, expression of a shorter
regulatory form of MAVS, which can suppress IFN-I secretion, is not present; Aim2: non-coding ribosomal RNA,
like 5S RNA in SLE patients, is oxidized and promotes ribosomal skipping; and Aim 3: performing ribosomal
profiling of SLE T cells will allow us to understand why oxidative stress associated with MAVS oligomerization
limits the translation of regulatory forms of innate immunity associated proteins.

## Key facts

- **NIH application ID:** 9966858
- **Project number:** 5R01AR073282-03
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Iwona Agnieszka Koenig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,660
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966858

## Citation

> US National Institutes of Health, RePORTER application 9966858, Ribosomal Skipping Under Oxidative Stress in SLE (5R01AR073282-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966858. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*