Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.
Transcriptome analysis of alternative splicing events regulated by SRSF10 reveals position-dependent splicing modulation.
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DOI：
10.1093/nar/gkt1387
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Zhou X;Wu W;Li H;Cheng Y;Wei N;Zong J;Feng X;Xie Z;Chen D;Manley JL;Wang H;Feng Y
已知剪接因子SRSF 10作为序列特异性剪接激活剂起作用。在这里，我们使用RNA-seq结合生物信息学分析来确定鸡细胞中SRSF 10调控的广泛剪接网络。我们发现SRSF 10促进外显子包含和排除。基序分析显示，SRSF 10结合盒外显子与外显子包含，而下游组成性外显子内的SRSF 10的结合与外显子排除。通过在两个小基因构建体中潜在的SRSF 10结合基序的诱变进一步证明了这种位置效应。在功能上，许多SRSF 10验证的替代外显子与应激和细胞凋亡的途径有关。与此观察结果一致，SRSF 10表达缺失的细胞比对照细胞更容易受到内质网应激诱导的凋亡。重要的是，在敲除细胞中重建的SRSF 10恢复了野生型剪接模式，并大大挽救了应激相关的缺陷。总之，我们的研究结果提供了对SRSF 10调节的体内选择性剪接事件的机制性见解，并证明了SRSF 10在应激条件下细胞存活中起着至关重要的作用。
Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Motif analysis revealed that SRSF10 binding to cassette exons was associated with exon inclusion, whereas the binding of SRSF10 within downstream constitutive exons was associated with exon exclusion. This positional effect was further demonstrated by the mutagenesis of potential SRSF10 binding motifs in two minigene constructs. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Consistent with this observation, cells depleted of SRSF10 expression were far more susceptible to endoplasmic reticulum stress-induced apoptosis than control cells. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1310607110
发表时间：
2013-07-16
影响因子：
11.1
作者：
Li, Huang;Wang, Zhijia;Feng, Ying
通讯作者：
Feng, Ying
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
7.2
作者：
Perry, Mary Ellen
通讯作者：
Perry, Mary Ellen
DOI：
10.1196/annals.1391.005
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Akerfelt, Malin;Trouillet, Diane;Sistonen, Lea
通讯作者：
Sistonen, Lea