TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.
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.
Lee
Kuo-Ming
KM
Institute of Biomedical Sciences, Academia Sinica, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsu
Ia-Wen
IaW
Tarn
Woan-Yuh
WY
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; C122111:NXF1 protein, human; D029543:Nucleocytoplasmic Transport Proteins; D012322:RNA Precursors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C475774:THRAP3 protein, human; D014157:Transcription Factors