A transcriptomic census reveals that Rbfox contributes to a broad but selective recapitulation of peripheral tissue splicing patterns in the thymus
A transcriptomic census reveals that Rbfox contributes to a broad but selective recapitulation of peripheral tissue splicing patterns in the thymus
复制标题
转录组普查表明，Rbfox 有助于胸腺中周围组织剪接模式的广泛但选择性的重演
DOI：
10.1101/2020.03.06.980870
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Jansen K
中科院分区：
文献类型：
--
作者：
Jansen K
胸腺上皮细胞（TEC）控制对病原体反应但对自身耐受的T细胞库的选择。虽然已知该过程涉及几乎整个蛋白质编码基因库的混杂表达，但TEC重演外周同种型的程度以及它们这样做的机制在很大程度上仍然未知。我们进行了第一次组装为基础的转录本结构和剪接因子（SF）的表达在小鼠髓质TEC（mTEC）和21外周组织的转录本普查。成熟的mTEC表达60.1%的所有蛋白质编码的转录本，超过检测到的任何外周组织。然而，对于具有组织限制性表达的基因，我们发现mTEC产生的同种型比相关外周组织少。外显子包含的分析显示，在mTEC的脑特异性微外显子的情况下。我们没有发现异常数量的新的转录本在TEC和显示thatAire，促进混杂基因表达，促进长转录本的使用，但只有有限的影响选择性剪接在mTEC。对mTEC中SF表达的综合评估鉴定了一小组非混杂表达的SF基因，其中我们证实RBFOX与AIRE一起存在于mTEC细胞核中。使用条件性功能丧失的方法，我们表明，Rbfox2促进mTEC的发展和调节混杂表达基因的选择性剪接。这些数据表明，TEC重新启动少量的外周SF，包括Rbfox家族的成员，以产生广泛但选择性的外周剪接异构体库的代表。
Thymic epithelial cells (TEC) control the selection of a T-cell repertoire reactive to pathogens but tolerant of self. While this process is known to involve the promiscuous expression of virtually the entire protein-coding gene repertoire the extent to which TEC recapitulate peripheral isoforms, and the mechanisms by which they do so, have remained largely unknown. We performed the first assembly-based transcriptomic census of transcript structures and splicing factor (SF) expression in mouse medullary TEC (mTEC) and 21 peripheral tissues. Mature mTEC expressed 60.1% of all protein-coding transcripts, more than was detected in any of the peripheral tissues. However, for genes with tissue-restricted expression, we found that mTEC produced fewer isoforms than did the relevant peripheral tissues. Analysis of exon inclusion revealed an absence of brain-specific micro-exons in mTEC. We did not find unusual numbers of novel transcripts in TEC and show thatAire, the facilitator of promiscuous gene expression, promotes usage of long transcripts but has only a limited impact on alternative splicing in mTEC. Comprehensive assessment of SF expression in mTEC identified a small set of non-promiscuously expressed SF genes amongst which we confirmed RBFOX to be present with AIRE in mTEC nuclei. Using a conditional loss of function approach, we show thatRbfox2promotes mTEC development and regulates the alternative splicing of promiscuously expressed genes. These data indicate that TEC recommission a small number of peripheral SFs, including members of the Rbfox family, to generate a broad but selective representation of the peripheral splice isoform repertoire.
登录
查看更多内容
影响因子：
8.8
作者：
Weyn-Vanhentenryck SM;Mele A;Yan Q;Sun S;Farny N;Zhang Z;Xue C;Herre M;Silver PA;Zhang MQ;Krainer AR;Darnell RB;Zhang C
通讯作者：
Zhang C
影响因子：
5.8
作者：
Juan-Mateu J;Villate O;Eizirik DL
通讯作者：
Eizirik DL
影响因子：
14.2
作者：
Ng, B;Yang, F;Yang, XF
通讯作者：
Yang, XF
影响因子：
4.5
作者：
Damianov, Andrey;Black, Douglas L.
通讯作者：
Black, Douglas L.
B7S3 作为 T 细胞新型负调节因子的表征1
影响因子：
4.4
作者：
Yang Yang;Xikui K. Liu;Thang Nguyen;C. Bishop;D. Graf;C. Dong
通讯作者：
C. Dong