RBM3 regulates temperature sensitive miR-142-5p and miR-143 (thermomiRs), which target immune genes and control fever

Wong, Justin J.-L., Au, Amy Y.M., Gao, Dada, Pinello, Natalia, Kwok, Chau-To, Thoeng, Annora, Lau, Katherine A., Gordon, Jane E.A., Schmitz, Ulf, Feng, Yue, Nguyen, Trung V., Middleton, Robert, Bailey, Charles G., Holst, Jeff, Rasko, John E.J., and Ritchie, William (2016) RBM3 regulates temperature sensitive miR-142-5p and miR-143 (thermomiRs), which target immune genes and control fever. Nucleic Acids Research, 44 (6). pp. 2888-2897.

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Abstract

Fever is commonly used to diagnose disease and is consistently associated with increased mortality in critically ill patients. However, the molecular controls of elevated body temperature are poorly understood. We discovered that the expression of RNA-binding motif protein 3 (RBM3), known to respond to cold stress and to modulate microRNA (miRNA) expression, was reduced in 30 patients with fever, and in THP-1-derived macrophages maintained at a fever-like temperature (40°C). Notably, RBM3 expression is reduced during fever whether or not infection is demonstrable. Reduced RBM3 expression resulted in increased expression of RBM3-targeted temperature-sensitive miRNAs, we termed thermomiRs. ThermomiRs such as miR-142–5p and miR-143 in turn target endogenous pyrogens including IL-6, IL6ST, TLR2, PGE2 and TNF to complete a negative feedback mechanism, which may be crucial to prevent pathological hyperthermia. Using normal PBMCs that were exogenously exposed to fever-like temperature (40°C), we further demonstrate the trend by which decreased levels of RBM3 were associated with increased levels of miR-142–5p and miR-143 and vice versa over a 24 h time course. Collectively, our results indicate the existence of a negative feedback loop that regulates fever via reduced RBM3 levels and increased expression of miR-142–5p and miR-143.

Item ID: 68989
Item Type: Article (Research - C1)
ISSN: 1362-4962
Copyright Information: © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC 1061906, NHMRC 1080530
Date Deposited: 09 Jun 2022 02:24
FoR Codes: 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310504 Epigenetics (incl. genome methylation and epigenomics) @ 50%
31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310208 Translational and applied bioinformatics @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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