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RNA-binding proteins control gene expression and cell fate in the immune system

Abstract

RNA-binding proteins (RBPs) are essential for the development and function of the immune system. They interact dynamically with RNA to control its biogenesis and turnover by transcription-dependent and transcription-independent mechanisms. In this Review, we discuss the molecular mechanisms by which RBPs allow gene expression changes to occur at different speeds and to varying degrees, and which RBPs regulate the diversity of the transcriptome and proteome. These proteins are nodes for integration of transcriptional and signaling networks and are intimately linked to intermediary metabolism. They are essential components of regulatory feedback mechanisms that maintain immune tolerance and limit inflammation. The role of RBPs in malignancy and autoimmunity has led to their emergence as targets for the development of new therapeutic modalities.

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Fig. 1: RBPs control the life of mRNA.

Marina Spence/Springer Nature.

Fig. 2: RNA granules are assembled in lymphocytes.

Marina Spence/Springer Nature.

Fig. 3: ZFP36 regulation of immune-cell activation.

Marina Spence/Springer Nature.

Fig. 4: RBPs mediate TORC-dependent regulation of cell metabolism.

Marina Spence/Springer Nature.

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Acknowledgements

We thank E. Glasmacher for allowing us to discuss her unpublished findings, and our many colleagues who have provided feedback and support during our preparation of this manuscript. We also thank E. Werbenko for providing images for Fig. 2. The Biotechnology and Biological Sciences Research Council, the Medical Research Council, Bloodwise and Wellcome support work in M.T.'s laboratory.

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Turner, M., Díaz-Muñoz, M.D. RNA-binding proteins control gene expression and cell fate in the immune system. Nat Immunol 19, 120–129 (2018). https://doi.org/10.1038/s41590-017-0028-4

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