Department of Neurology, Philipps-University Marburg, Marburg, Germany; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
Department of Neurology, Philipps-University Marburg, Marburg, Germany; Max-Planck-Institute for Terrestrial Microbiology, Marburg, Germany.
Gene. 2020 Nov 15;760:145021. doi: 10.1016/j.gene.2020.145021. Epub 2020 Aug 4.
Human B cell activating factor (TNFSF13B, BAFF) is a tumor necrosis factor superfamily member. Binding its unique receptor (TNFRSF13C, BAFF-R) mediates gene expression and cell survival in B cells via activation of NFκB pathway. Furthermore, there is data indicating a role in T cell function. A functionally inhibitory isoform (ΔBAFF) resulting from the deletion of exon 3 in the TNFSF13B pre-RNA has already been reported. However, data on the complexity of post-transcriptional regulation is scarce. Here, we report molecular cloning of nine TNFSF13B transcript variants resulting from alternative splicing of the TNFSF13B pre-mRNA including BAFFX1. This variant is characterized by a partial retention of intron 3 of the TNFSF13B gene causing the appearance of a premature stop codon. We demonstrate the expression of the corresponding BAFFX1 protein in Jurkat T cells, in ex vivo human immune cells and in human tonsillar tissue. Thereby we contribute to the understanding of TNFSF13B gene regulation and reveal that BAFF is regulated through a post-transcriptional mechanism to a greater extent than reported to date.
人 B 细胞激活因子（TNFSF13B，BAFF）是肿瘤坏死因子超家族成员。其独特受体（TNFRSF13C，BAFF-R）的结合通过 NFκB 途径的激活介导 B 细胞中的基因表达和细胞存活。此外，有数据表明其在 T 细胞功能中起作用。已经报道了一种功能性抑制同种型（ΔBAFF），其是 TNFSF13B 前 RNA 中第 3 外显子缺失的结果。然而，关于转录后调控复杂性的数据很少。在这里，我们报告了通过 TNFSF13B 前 mRNA 的选择性剪接产生的九个 TNFSF13B 转录变体的分子克隆，包括 BAFFX1。该变体的特征是 TNFSF13B 基因的内含子 3 部分保留，导致出现过早的终止密码子。我们证明了相应的 BAFFX1 蛋白在 Jurkat T 细胞、体外人类免疫细胞和人扁桃体组织中的表达。由此，我们有助于理解 TNFSF13B 基因调控，并揭示 BAFF 通过转录后机制受到的调控比迄今为止报道的更为广泛。
