The RNA-binding protein HuR is essential for the B cell antibody response.

The RNA-binding protein HuR is essential for the B cell antibody response.
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DOI:
10.1038/ni.3115
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发表时间:
2015-04
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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在B细胞中,需要RNA结合蛋白HuR(Elavl 1)对mRNA进行转录后调节,以进行生发中心反应和产生响应于T非依赖性抗原的类别转换抗体。HuR缺陷B细胞中RNA亚型、丰度和翻译的全转录组检查,以及HuR-RNA相互作用的直接测量,显示HuR依赖性mRNA剪接影响数百种转录物,包括二氢硫辛酰胺S-琥珀酰转移酶(Dlst),2-酮戊二酸脱氢酶复合物(αKGDH)的亚基。在HuR不存在的情况下,线粒体代谢缺陷导致大量的活性氧和B细胞死亡。我们的研究显示了转录后过程如何控制B细胞增殖和分化所需的能量代谢平衡。
Post-transcriptional regulation of mRNA by the RNA binding protein HuR (Elavl1) is required in B cells for the germinal centre reaction and for the production of class-switched antibodies in response to T-independent antigens. Transcriptome-wide examination of RNA isoforms, abundance and translation in HuR-deficient B cells, together with direct measurements of HuR-RNA interaction, revealed that HuR-dependent mRNA splicing affects hundreds of transcripts including the dihydrolipoamide S-succinyltransferase (Dlst), a subunit of the 2-oxoglutarate dehydrogenase complex (αKGDH). In the absence of HuR, defective mitochondrial metabolism results in high amounts of reactive oxygen species and B cell death. Our study shows how post-transcriptional processes control the balance of energy metabolism required for B cell proliferation and differentiation.
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