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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

ABSTRACT: Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

PROVIDER: PRJNA1002969 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25512121_1.fastq.gz	Fastqsanger.gz
	SRR25512121_2.fastq.gz	Fastqsanger.gz
	SRR25512122_1.fastq.gz	Fastqsanger.gz
	SRR25512122_2.fastq.gz	Fastqsanger.gz
	SRR25512123_1.fastq.gz	Fastqsanger.gz

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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

Project description:Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

Project description:Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

Project description:Dysregulation of mast cell activation can lead to allergic and anaphylactic reactions. Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) is critical in controlling immune cell responses, including mast cell functionality. The Regnase family of RBPs plays a central role in regulating gene expression and controlling immune responses in both lymphoid and myeloid cells. However, what is the functional role of Regnase proteins in mast cells remains to be understood. Using different approaches of Regnase proteins depletion and deletion as well as overexpression by mRNA delivery, we found that Regnase-1 is a powerful negative regulator of mast cell proliferation, survival and ability to produce inflammatory cytokines. On the other hand, Regnase-3 was essential to modulate Regnase-1 expression in mast cells by direct targeting of the 3’-untranslated region of Regnase-1, leading to the destabilization of the Zc3h12a mRNA. Regnase-1 deletion had widespread effect on mast proliferation and survival even in the absence of stimulation and was at least in part linked to specific nuclear functions of Regnase-1 in modulating the ability of mast cells to withstand DNA damage. Overall, we describe the importance of Regnase proteins in modulating mast cell homeostatic and inflammatory responses and we describe the impact of Regnase-1 in the maintenance of genome stability.

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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

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Crosstalk between the RNA-binding proteins Regnase-1 and -3 shapes mast cell survival and cytokine expression

Project description:Post-transcriptional regulation of immune-related transcripts by RNA-binding proteins (RBPs) impacts immune cell responses, including mast cell functionality. Despite their importance in immune regulation, the functional role of most RBPs remains to be understood. By manipulating the expression of specific RBPs in murine mast cells, coupled with mass spectrometry and transcriptomic analyses, we found that the Regnase family of proteins acts as a potent regulator of mast cell physiology. Specifically, Regnase-1 is required to maintain basic cell proliferation and survival, while both Regnase-1 and -3 cooperatively regulate the expression of inflammatory transcripts upon activation, with Tnf being a primary target in both human and mouse cells. Further, Regnase-3 directly interacts with Regnase-1 in mast cells and is necessary to restrain Regnase-1 expression through the destabilization of its transcript. Overall, our study identifies protein interactors of endogenously expressed Regnase factors, characterizes the regulatory interplay between Regnase family members in mast cells, and establishes their role in the control of mast cell homeostasis and inflammatory responses.

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Crosstalk between Regnase-1 and -3 shapes mast cell survival and cytokine expression

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The difference between intraepithelial mast cells and lamina propria mast cells

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