Objective:

To explore how local metabolic stress influences RNA methylation and contributes to pathogenic cellular changes in rheumatoid arthritis (RA).

Approach:

• Metabolic Environment Analysis: Examined the impact of local hypoxia, glycolytic flux, lactate accumulation, mitochondrial dysfunction, oxidative stress, and lipid metabolic imbalance on RNA methylation regulators.
• Cellular Mechanism Investigation: Investigated the roles of RNA methylation in fibroblast-like synoviocytes, macrophages, T cells, and neutrophils in the context of RA.
• Integration of Epitranscriptomics: Discussed the integration of RNA methylation with non-coding RNA networks, extracellular vesicle signaling, and regulated cell death pathways.

Key Findings:

• RNA methylation is a critical post-transcriptional regulator in immune and stromal cell adaptation, particularly in fibroblast-like synoviocytes, macrophages, T cells, and neutrophils.
• Metabolic alterations in the synovium support pathogenic proliferation and enhance resistance to stress-induced cell death.
• RNA methylation stabilizes glycolytic fitness, invasive behavior, and inflammatory polarization in various cell types, including FLS and macrophages.

Interpretation:

RNA methylation serves as a dynamic interface that connects metabolic stress to pathogenic adaptations in rheumatoid arthritis.

Limitations:

• Further exploration is needed to understand how metabolic stress directly influences epitranscriptomic remodeling in RA.
• Most studies have concentrated on the downstream effects of RNA methylation rather than its regulatory mechanisms.

Conclusion:

Targeting metabolic stress and RNA methylation-dependent adaptation may offer new avenues for intervention in rheumatoid arthritis.