Abstract
Post‐transcriptional regulation of cytokine production is crucial to ensure appropriate immune responses. We previously demonstrated that poly‐rC‐binding protein‐1 (PCBP1) can act as a trans‐acting factor to stabilize transcripts encoding sortilin, which mediates cytokine trafficking. Here, we report that PCBP2, which strongly resembles PCBP1, can stabilize sortilin transcripts in macrophages using the same mechanism employed by PCBP1. PCBP2 recognized the C‐rich element in the 3′ UTR of sortilin mRNA, and PCBP2 knockdown decreased sortilin transcripts, indicating that PCBP2 stabilizes sortilin mRNA by binding to its 3′ UTR. Zn2+ reversibly inhibited the nucleotide binding ability of PCBP2 in vitro. These findings suggest that both PCBP2 and PCBP1 may control the stability of sortilin transcripts by sensing intracellular Zn2+ levels in immune cells.
Highlights
Recognition of pathogen-associated molecular patterns by pattern-recognition receptors (PRRs) and the subsequent production of proinflammatory cytokines play an important role in the innate immune system [1]
A recent study demonstrated that Pcbp1-deficient mouse embryos die at the peri-implantation stage [7], Abbreviations cDC, conventional dendritic cell; CRE, C-rich element; PCBP, Poly-rC-binding protein; pDC, plasmacytoid dendritic cell; PRR, patternrecognition receptor; RBP, RNA-binding protein; TLR, Toll-like receptor
We describe the interaction of PCBP2 with the CRE of the 30 UTR of sortilin mRNA, which leads to the stabilization of the sortilin mRNA
Summary
Recognition of pathogen-associated molecular patterns by pattern-recognition receptors (PRRs) and the subsequent production of proinflammatory cytokines play an important role in the innate immune system [1]. We previously demonstrated that PCBP1 is involved in the regulation of sortilin, which mediates cytokine trafficking via stabilization of its mRNA [17]. We measured the protein expression levels of PCBP1 and PCBP2 in multiple types of immune cells and examined the involvement of PCBP2 in the stabilization of sortilin mRNA.
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