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RP-11, a novel male-specific long non-coding RNA, controls metabolic and immune pathways that may protect against autoimmunity 2489

Year: 2025
Type: article
Abstract: Description Non-coding RNA (ncRNA) are transcripts that make up 98% of our gene expression that do not code for proteins but may still serve a diverse array of functions and even be important in sex-biased pathologies. Xist, a ncRNA known for its putative role in female development through X-chromosome inactivation shuts down one copy of the X-chromosome. On that chromosome are interferon and NFκB-mediated immunomodulatory genes, and when Xist is overexpressed, it can lead to systemic autoimmune disease. Outside of Xist, there are very few other studies exploring links between sex-biased ncRNA and sex-biased disease. ncRNA are also implicated in regulating both glucose and lipid metabolism, but their role in sex differences in metabolism remains unclear too. This may be due to the increased importance laid upon sex hormones in sex bias. We hope to bridge this gap in knowledge by exploring another ncRNA, the human male-specific RP11-424G14.1 (RP11). To date, this is the first study that is exploring the function of RP11, a ncRNA of 2,666 bp length located on the Y chromosome, or GRCh37:CM000686.1 in the GRch37 human genome assembly. We show that RP11 is male-biased, promotes senescence, modulates lipid metabolism, and is protective against TNFα-induced inflammatory signaling likely through insulin growth factor binding protein 3 (IGFBP3). The diverse regulatory functions of RP11 and Xist show a need for greater study into ncRNA when evaluating the mechanisms of sex-biased pathophysiology. Funding Sources NIH R01 AR078781 Topic Categories Basic Autoimmunity (BA)
DOI: 10.1093/jimmun/vkaf283.401
Language: English
Subfield: Cancer Research
Open Access status: bronze
OpenAlex ID: W4416447296
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