Institute of Biomedical Sciences, Academia Sinica, College of Medicine, National Taiwan University, Taipei, Taiwan.
Nucleic Acids Res. 2010 Jun;38(10):3340-50. doi: 10.1093/nar/gkq017. Epub 2010 Jan 31.
TRAP150 has been identified as a subunit of the transcription regulatory complex TRAP/Mediator, and also a component of the spliceosome. The exact function of TRAP150, however, remains unclear. We recently identified TRAP150 by its association with the mRNA export factor TAP. TRAP150 contains an arginine/serine-rich domain and has sequence similarity with the cell death-promoting transcriptional repressor BCLAF1. We found that TRAP150 co-localizes with splicing factors in nuclear speckles, and is required for pre-mRNA splicing and activates splicing in vivo. TRAP150 remains associated with the spliced mRNA after splicing, and accordingly, it interacts with the integral exon junction complex. Unexpectedly, when tethered to a precursor mRNA, TRAP150 can trigger mRNA degradation in the nucleus. However, unlike nonsense-mediated decay, TRAP150-mediated mRNA decay is irrespective of the presence of upstream stop codons and occurs in the nucleus. Moreover, TRAP150 activates pre-mRNA splicing and induces mRNA degradation by its separable functional domains. Therefore, TRAP150 represents a multi-functional protein involved in nuclear mRNA metabolism.
TRAP150 被鉴定为转录调控复合物 TRAP/Mediator 的亚基，也是剪接体的组成部分。然而，TRAP150 的确切功能仍不清楚。我们最近通过其与 mRNA 输出因子 TAP 的关联鉴定了 TRAP150。TRAP150 含有一个精氨酸/丝氨酸丰富的结构域，与促进细胞死亡的转录抑制因子 BCLAF1 具有序列相似性。我们发现 TRAP150 与核斑点中的剪接因子共定位，并且是剪接前体 RNA 所必需的，并且在体内激活剪接。TRAP150 在剪接后仍然与拼接的 mRNA 结合，因此与完整的外显子连接复合物相互作用。出乎意料的是，当与前体 mRNA 连接时，TRAP150 可以在核内触发 mRNA 降解。然而，与无意义介导的衰变不同，TRAP150 介导的 mRNA 降解与上游终止密码子的存在无关，并且发生在核内。此外，TRAP150 通过其可分离的功能结构域激活剪接前体 RNA 的剪接并诱导 mRNA 降解。因此，TRAP150 代表一种参与核 mRNA 代谢的多功能蛋白。
