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Fragile X messenger ribonucleoprotein modulates IL-6 induction and inflammatory cell death in macrophages

Macha, B. N.; Weindel, C. G.; Fischer, T.; Watson, R. O.; Ho, L. A.; Vail, K. J.

2026-04-01 immunology
10.64898/2026.03.30.712626 bioRxiv
Show abstract

RNA-binding proteins are key players in determining the fate of mRNA. One such RNA binding protein, Fragile X messenger ribonucleoprotein (FMRP), has an established role in RNA transcription, metabolism, translation, and degradation in the brain and reproductive system. Although FMRP is expressed in immune cells, little is known about how FMRP influences immune cell mRNA transcript outcomes. Here, we show that macrophage infection with the intracellular pathogen Listeria monocytogenes induces FMRP translocation from the cytoplasm to the nucleus. We show that infected macrophages lacking FMRP have impaired Il6 induction in response to L. monocytogenes infection. Finally, we show that macrophages lacking FMRP have increased susceptibility to inflammatory cell death. Together, these data implicate FMRP in modulating proinflammatory gene expression during bacterial infection.

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