Abstract
Post-transcriptional regulation is a fundamental process in gene expression that has a role in diverse cellular processes, including immune responses. A core concept underlying post-transcriptional regulation is that protein abundance is not solely determined by transcript abundance. Indeed, transcription and translation are not directly coupled, and intervening steps occur between these processes, including the regulation of mRNA stability, localization and alternative splicing, which can impact protein abundance. These steps are controlled by various post-transcription factors such as RNA-binding proteins and non-coding RNAs, including microRNAs, and aberrant post-transcriptional regulation has been implicated in various pathological conditions. Indeed, studies on the pathogenesis of autoimmune and inflammatory diseases have identified various post-transcription factors as important regulators of immune cell-mediated and target effector cell-mediated pathological conditions. This Review summarizes current knowledge regarding the roles of post-transcriptional checkpoints in autoimmunity, as evidenced by studies in both haematopoietic and non-haematopoietic cells, and discusses the relevance of these findings for developing new anti-inflammatory therapies.
Key points
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Post-transcriptional regulation of gene expression is an important step in controlling various cellular processes, including immune-related processes, and disruption of post-transcriptional regulation can lead to aberrant cell responses.
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Redundant, cooperative and antagonistic post-transcriptional regulators control the expression of immune-related mRNA transcripts, enabling the fine-tuning of inflammatory responses.
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Post-transcriptional checkpoints are involved in the regulation of antibody-mediated autoimmunity and T cell-mediated autoimmunity.
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Post-transcriptional checkpoints in non-haematopoietic cells might also contribute to autoimmune manifestations.
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Specific post-transcriptional regulators are abnormally expressed or function aberrantly in various systemic or organ-specific autoimmune conditions.
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Additional mechanistic and translational research is needed to therapeutically harness the post-transcriptional pathway.
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This work has been supported as part of France 2030 program “ANR-11-IDEX-0003”, from the OI HEALTHI of the Université Paris-Saclay.
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Bechara, R., Vagner, S. & Mariette, X. Post-transcriptional checkpoints in autoimmunity. Nat Rev Rheumatol 19, 486–502 (2023). https://doi.org/10.1038/s41584-023-00980-y
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DOI: https://doi.org/10.1038/s41584-023-00980-y
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