Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Splicing TRAP150 contains an RS domain and is associated with several precursor mRNA (pre-mRNA) splicing factors (Li et al., 2003; Lee et al., 2010). Moreover, TRAP150 was also reported to interact with the domains that provide links between transcription and splicing, such as the WW domains of pinin and the FF domains of CA150 (Smith et al., 2004; Ingham et al., 2005). Therefore TRAP150 has been proposed to function in coupling of transcription and pre-mRNA processing (Auboeuf et al., 2005). This possibility was supported by independent biochemical analyses of mRNA ribonucleoprotein (mRNP) complexes. Firstly, TRAP150 was identified as a component of mRNPs; its association with mRNAs was splicing- and cap-binding complex (CBC)-independent (Merz et al., 2007). Moreover, TRAP150 was detected in the spliceosomal complex B, which is a fully assembled splicing complex prior to the catalytic step of splicing (Bessonov et al., 2008; Wahl et al., 2009). Finally, experimental evidence showed that overexpression of TRAP150 activated the splicing of a reporter pre-mRNA, while knockdown of TRAP150 impaired the splicing (Lee et al., 2010), indicating the role of TRAP150 in facilitating pre-mRNA splicing.
Other pre-mRNA processing events TRAP150 and its analog BCLAF1 are associated with SNIP1 (Smad nuclear interacting protein 1), pinin and SkIP (Ski-interacting protein) to form the SNIP1/SkIP-associated RNA processing (SNARP) complex. The SNARP regulates the expression level of cyclin D1 probably by recruiting U2AF65 to its pre-mRNA (Bracken et al., 2008; Witzel et al., 2010). To date, whether TRAP150 is directly involved in alternative pre-mRNA splicing still remains to be investigated. However, TRAP150 may modulate splicing through protein-protein interactions. In resting T cells, TRAP150 binds to phosphorylated PTB-associated splicing factor (PSF), which results in steric hindrance of the RNA recognition motifs of PSF. Upon T cell activation, de-phosphorylated PSF is dissociated from TRAP150 and therfore could regulate the alternative splicing of CD45 transcripts (Heyd et al., 2010). In addition to splicing, TRAP150 may participate in mRNA degradation. When tethered to a reporter precursor mRNA, TRAP150 could promote the degradation of the spliced mRNA, which occurs in a translation-independent manner and in the nucleus (Lee et al., 2010).
NCBI: 9967 MIM: 603809 HGNC: 22964 Ensembl: ENSG00000054118
dbSNP: 9967 ClinVar: 9967 TCGA: ENSG00000054118 COSMIC: THRAP3
Kuo-Ming Lee ; Woan-Yuh Tarn
THRAP3 (thyroid hormone receptor associated protein 3)
Atlas Genet Cytogenet Oncol Haematol. 2012-03-01
Online version: http://atlasgeneticsoncology.org/gene/42960/thrap3