The strand-selective regulation of miR-155 response to lipopolysaccharide by CELF2, FUBP1 and KSRP proteins

Yoon, J. S.; Baksh, A.; Chaberlain, T. C.; Mui, A.

doi:10.1101/2025.03.05.641704

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bioRxiv · 10.1101/2025.03.05.641704

The strand-selective regulation of miR-155 response to lipopolysaccharide by CELF2, FUBP1 and KSRP proteins

Yoon, J. S.·Baksh, A.·Chaberlain, T. C.·Mui, A.

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Abstract

The microRNA-155 exists in two forms, miR-155-5p and miR-155-3p, produced from either strand of the double-stranded precursor of miR-155. The more abundant and better-studied miR-155-5p has been implicated in many biological processes with dysregulated expression occurring in human diseases. miR-155-5p plays an essential role in supporting inflammatory responses in macrophages. Activating macrophages with lipopolysaccharide elevates miR-155-5p, while the anti-inflammatory cytokine interleukin-10 reduces miR-155-5p levels. Recently, miR-155-3p has also been suggested to participate in macrophage function, although its specific role is unclear. We found that LPS stimulation of macrophages results first in the elevation of miR-155-3p levels, followed by an increase in miR-155-5p levels. In this paper, we explore the mechanisms involved in the maturation of the pre-miR-155 to either miR-155-5p or miR-155-3p. We describe the contribution of three RNA-binding proteins, CELF2, FUBP1 and KSRP, to pre-miR-155 processing. Our data suggests CELF2 regulates miR-155-5p/miR-155-3p strand selection. FUBP1 may support the expression of miR-155-3p for specific subcellular functions, while KSRP appears to inhibit both miR-155-5p and miR-155-3p maturation without altering the relative expression of each strand.

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Yoon, J. S., Baksh, A., Chaberlain, T. C., Mui, A.. 2025-03-11. The strand-selective regulation of miR-155 response to lipopolysaccharide by CELF2, FUBP1 and KSRP proteins. https://doi.org/10.1101/2025.03.05.641704

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