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bioRxiv · 10.1101/2025.06.19.660645

Alternative Polyadenylation Releases PCBP1-Mediated Suppression of CFIm25 During Macrophage Differentiation

Mendoza Martin, M. d. P.·Mostafa, S. M.·Barua, A.·Moore, C.·Mukherjee, S.
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Abstract

CFIm25, a key component of the CFIm complex needed for mRNA 3 end processing, shows increased protein expression during monocyte-to-macrophage differentiation despite stable mRNA levels. We demonstrate that PCBP1 suppresses CFIm25 translation in monocytes by binding to its long 3UTR. During differentiation, alternative polyadenylation generates a shorter CFIm25 3UTR lacking PCBP1 binding sites. RNA immunoprecipitation confirms PCBP1 binding to the long 3UTR, while ribosome association analysis shows enhanced translation without this interaction. PCBP1 knockdown increases CFIm25 protein specifically in undifferentiated cells and induces macrophage differentiation markers without stimulation. These findings reveal how alternative polyadenylation controls CFIm25 expression during immune cell differentiation by modulating RNA-binding protein interactions and provide insight into post-transcriptional regulation of RNA processing factors.

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Mendoza Martin, M. d. P., Mostafa, S. M., Barua, A., Moore, C., Mukherjee, S.. 2025-06-22. Alternative Polyadenylation Releases PCBP1-Mediated Suppression of CFIm25 During Macrophage Differentiation. https://doi.org/10.1101/2025.06.19.660645

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