# Explore the involvement of tRNA in the pathophysiology of antisynthetase syndrome

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2024 · $242,880

## Abstract

Project Summary
Antisynthetase syndrome (ASSD) is a chronic autoimmune disorder characterized by myositis and interstitial
lung disease (ILD). A key feature of ASSD is the presence of autoantibodies against aminoacyl-tRNA synthe-
tases (aaRSs), among which histidyl-tRNA synthetase (HARS or HisRS) causing anti-Jo-1 antibodies is the most
common. aaRSs are the enzymes that attach amino acids to their appropriate tRNA and are thus essential
components of the intracellular translation machinery. Interestingly, some aaRSs are also secreted and function
extracellularly to regulate inflammation and immune responses. However, the mechanisms by which aaRSs are
released from cells, become targets of autoimmunity, and cause symptoms are not well understood. Importantly,
tRNA, a key partner of aaRS, has not been considered at all in the context of ASSD. There is growing evidence
suggesting the involvement of endosomal Toll-like receptor TLR7 and type I interferon (IFN-I) signaling in sus-
taining and spreading inflammation in the autoimmune disease. The ligands that activate TLR7 are single strand
RNAs (ssRNAs). Therefore, we hypothesize that tRNAs or tRNA fragments bound to aaRSs play critical roles in
the pathogenesis of ASSD. We propose a two-year project to explore the hypothesis using ASSD-relevant cells
and to generate a novel and clinically relevant animal model for mechanistic study and future therapeutic devel-
opment. The results obtained from this study would uncover a previously unrecognized involvement of tRNAs in
the pathogenesis of ASSD and suggest new targets for therapeutic development of the disease.

## Key facts

- **NIH application ID:** 10889843
- **Project number:** 1R21AR083063-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Taisuke Kanaji
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $242,880
- **Award type:** 1
- **Project period:** 2024-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889843

## Citation

> US National Institutes of Health, RePORTER application 10889843, Explore the involvement of tRNA in the pathophysiology of antisynthetase syndrome (1R21AR083063-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10889843. Licensed CC0.

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