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RNA-binding proteins and RNA methylation in myeloid cells
Immunological Reviews ( IF 7.5 ) Pub Date : 2021-09-14 , DOI: 10.1111/imr.13025
Marian Bataclan 1 , Cristina Leoni 1 , Silvia Monticelli 1
Affiliation  

RNA-binding proteins (RBPs) regulate all aspects of the life of mRNA transcripts. They are critically important in regulating immune responses, most notably by restraining excessive inflammation that can potentially lead to tissue damage. RBPs are also crucial for pathogen sensing, for instance for the recognition of viral nucleic acids. Concordant with these central regulatory roles, the dysregulated activity of many RBPs can give rise to disease. The expression and function of RBPs are therefore highly controlled by an elaborate network of transcriptional, post-transcriptional and post-translational mechanisms, including the ability of different RBPs to cross-regulate each other's expression. With an emphasis on macrophages and mast cells, we review current knowledge on the role of selected RBPs that have been shown to directly impact the expression of inflammatory transcripts. By focusing specifically on proteins of the Regnase and ZFP36 family, as well as on factors involved in N6-methyladenosine (m6A) deposition and recognition, we discuss mechanism of action, regulatory feedback, and impact of these selected proteins on immune responses. Finally, we include examples of the role of m6A and RBPs in the recognition of viral RNAs. Overall, we provide a general overview of the impact of selected RBPs on the myeloid compartment, followed by a discussion of outstanding questions and challenges for the future.

中文翻译:

骨髓细胞中的 RNA 结合蛋白和 RNA 甲基化

RNA 结合蛋白 (RBP) 调节 mRNA 转录物生命的各个方面。它们对于调节免疫反应至关重要,尤其是通过抑制可能导致组织损伤的过度炎症。RBP 对于病原体传感也至关重要,例如对于病毒核酸的识别。与这些中枢调节作用一致,许多 RBP 的活性失调可能导致疾病。因此,RBP 的表达和功能受到转录、转录后和翻译后机制的复杂网络的高度控制,包括不同 RBP 交叉调节彼此表达的能力。我们重点关注巨噬细胞和肥大细胞,回顾了有关选定 RBP 作用的最新知识,这些 RBP 已被证明可直接影响炎症转录本的表达。通过特别关注 Regnase 和 ZFP36 家族的蛋白质,以及参与 N 6 -甲基腺苷 (m 6 A) 沉积和识别的因素,我们讨论了这些选定蛋白质的作用机制、调节反馈以及对免疫反应的影响。最后,我们提供了 m 6 A 和 RBP 在病毒 RNA 识别中的作用示例。总的来说,我们概述了选定的 RBP 对骨髓室的影响,然后讨论了未来的突出问题和挑战。
更新日期:2021-09-14
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