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TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.

ABSTRACT: 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.

SUBMITTER: Lee KM

PROVIDER: S-EPMC2879504 | biostudies-other | 2010 Jun

REPOSITORIES: biostudies-other

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TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.

Lee Kuo-Ming KM Hsu Ia-Wen IaW Tarn Woan-Yuh WY

Nucleic acids research 20100131 10

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 i ...[more]

PMID: 20123736

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Project description:In the present study, the spatial organization of intron-containing pre-mRNAs of Epstein-Barr virus (EBV) genes relative to location of splicing factors is investigated. The intranuclear position of transcriptionally active EBV genes, as well as of nascent transcripts, is found to be random with respect to the speckled accumulations of splicing factors (SC35 domains) in Namalwa cells, arguing against the concept of the locus-specific organization of mRNA genes with respect to the speckles. Microclusters of splicing factors are, however, frequently superimposed on nascent transcript sites. The transcript environment is a dynamic structure consisting of both nascent and released transcripts, i.e., the track-like transcript environment. Both EBV sequences of the chromosome 1 homologue are usually associated with the track, are transcriptionally active, and exhibit in most cases a polar orientation. In contrast to nascent transcripts (in the form of spots), the association of a post-transcriptional pool of viral pre-mRNA (in the form of tracks) with speckles is not random and is further enhanced in transcriptionally silent cells when splicing factors are sequestered in enlarged accumulations. The transcript environment reflects the intranuclear transport of RNA from the sites of transcription to SC35 domains, as shown by concomitant mapping of DNA, RNA, and splicing factors. No clear vectorial intranuclear trafficking of transcripts from the site of synthesis toward the nuclear envelope for export into the cytoplasm is observed. Using Namalwa and Raji cell lines, a correlation between the level of viral gene transcription and splicing factor accumulation within the viral transcript environment has been observed. This supports a concept that the level of transcription can alter the spatial relationship among intron-containing genes, their transcripts, and speckles attributable to various levels of splicing factors recruited from splicing factor reservoirs. Electron microscopic in situ hybridization studies reveal that the released transcripts are directed toward reservoirs of splicing factors organized in clusters of interchromatin granules. Our results point to the bidirectional intranuclear movement of macromolecular complexes between intron-containing genes and splicing factor reservoirs: the recruitment of splicing factors to transcription sites and movement of released transcripts from DNA loci to reservoirs of splicing factors.

Dataset Information

TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.

Publications

TRAP150 activates pre-mRNA splicing and promotes nuclear mRNA degradation.

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