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The RNA regulatory programs that govern lymphocyte development and function

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Abstract Lymphocytes require of constant and dynamic changes in their transcriptome for timely activation and production of effector molecules to combat external pathogens. Synthesis and translation of messenger (m)RNAs into these effector proteins is controlled both quantitatively and qualitatively by RNA binding proteins (RBPs). RBP‐dependent regulation of RNA editing, subcellular location, stability, and translation shapes immune cell development and immunity. Extensive evidences have now been gathered from few model RBPs, HuR, PTBP1, ZFP36, and Roquin. However, recently developed methodologies for global characterization of protein:RNA interactions suggest the existence of complex RNA regulatory networks in which RBPs co‐ordinately regulate the fate of sets of RNAs controlling cellular pathways and functions. In turn, RNA can also act as scaffolding of functionally related proteins modulating their activation and function. Here we review current knowledge about how RBP‐dependent regulation of RNA shapes our immune system and discuss about the existence of a hidden immune cell epitranscriptome. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications
Levels of post‐transcriptional regulation for gene expression, DNA mutagenesis, and control of protein function (created with BioRender.com)
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(a) Protein–RNA phase separation and assembly of RNA granules. A core of proteins with disordered domains and RNA is surrounded by a gel‐like phase with constant shuttle of RBPs and RNA subject to sensing of intracellular and extracellular cues. (b) Classical RNA binding proteins control the expression of glycolytic enzymes which fuel energy production and mRNA translation and protein synthesis for lymphocyte activation and proliferation upon antigen recognition. (c) Representation of glycolysis energy pathway with glycolytic enzymes with RNA binding moonlighting functions in red (created with BioRender.com)
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Methodologies for global identification of proteins with RNA binding properties, mapping of protein:RNA interactions, and spatial analysis of protein:RNA interaction in the cell (created with BioRender.com)
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