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边缘区B细胞区室的维持特别需要RNA结合蛋白ZFP36L1。

Maintenance of the marginal-zone B cell compartment specifically requires the RNA-binding protein ZFP36L1.

作者信息

Newman Rebecca, Ahlfors Helena, Saveliev Alexander, Galloway Alison, Hodson Daniel J, Williams Robert, Besra Gurdyal S, Cook Charlotte N, Cunningham Adam F, Bell Sarah E, Turner Martin

机构信息

Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.

Immune Receptor Activation Laboratory, The Francis Crick Institute, London, UK.

出版信息

Nat Immunol. 2017 Jun;18(6):683-693. doi: 10.1038/ni.3724. Epub 2017 Apr 10.

DOI:10.1038/ni.3724
PMID:28394372
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5438597/
Abstract

RNA-binding proteins of the ZFP36 family are best known for inhibiting the expression of cytokines through binding to AU-rich elements in the 3' untranslated region and promoting mRNA decay. Here we identified an indispensable role for ZFP36L1 as the regulator of a post-transcriptional hub that determined the identity of marginal-zone B cells by promoting their proper localization and survival. ZFP36L1 controlled a gene-expression program related to signaling, cell adhesion and locomotion; it achieved this in part by limiting expression of the transcription factors KLF2 and IRF8, which are known to enforce the follicular B cell phenotype. These mechanisms emphasize the importance of integrating transcriptional and post-transcriptional processes by RNA-binding proteins for maintaining cellular identity among closely related cell types.

摘要

ZFP36家族的RNA结合蛋白最为人所知的是，它们通过与3'非翻译区富含AU的元件结合来抑制细胞因子的表达，并促进mRNA降解。在这里，我们确定了ZFP36L1作为转录后枢纽调节因子的不可或缺的作用，该枢纽通过促进边缘区B细胞的正确定位和存活来决定其身份。ZFP36L1控制着一个与信号传导、细胞粘附和运动相关的基因表达程序；它部分是通过限制转录因子KLF2和IRF8的表达来实现的，已知这两种转录因子会强化滤泡B细胞表型。这些机制强调了RNA结合蛋白整合转录和转录后过程对于在密切相关的细胞类型中维持细胞身份的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6caf/5438597/4db64ba444cd/emss-71833-f008.jpg
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