poly(U)-binding-splicing factor PUF60 (60 kD poly(U)-binding-splicing factor, FUSE-binding protein-interacting repressor, FBP-interacting repressor, siah-binding protein 1, Siah-BP1, Ro-binding protein 1, RoBP1, PUF60, FIR, ROBPI, SIAHBP1)
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Function
- DNA- & RNA-binding protein
- involved in several nuclear processes including pre-mRNA splicing, apoptosis & transcription regulation
- in association with FUBP1, regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor
- acts as a transcriptional repressor through the core-TFIIH basal transcription facto
- represses FUBP1-induced transcriptional activation but not basal transcription
- decreases ERCC3 helicase activity
- does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells
- role in pre-mRNA splicing
- promotes splicing of an intron with weak 3'-splice site & pyrimidine tract in a cooperative manner with U2AF2
- role in apoptosis induction when overexpressed in HeLa cells
- isoform 6 failed to repress MYC transcription & inhibited FIR-induced apoptosis in colorectal cancer
- isoform 6 may contribute to tumor progression by enabling increased MYC expression & greater resistance to apoptosis in tumors than in normal cells
- modulates alternative splicing of several mRNAs
- binds to relaxed DNA of active promoter regions
- binds to the pyrimidine tract & 3'-splice site regions of pre-mRNA
- binding is enhanced in presence of U2AF2
- binds to Y5 RNA in association with TROVE2
- binds to poly(U) RNA
- associates with the spliceosome
- found in a complex with TROVE2 & Y5 RNA
- found in a complex with FUBP1 & far upstream element (FUSE) DNA segment
- interacts directly with ERCC3
- interacts with CDK7, GTF2H1 & SFRS11
Structure
- homodimer
- the third RNA recognition motif, called PUMP domain, is atypical & may rather mediate homodimerization &/or protein- protein interactions
- belongs to the RRM half pint family
- contains 3 RRM (RNA recognition motif) domains
Compartment
Alternative splicing
named isoforms=6
Expression
- isoform 2 is expressed in colonic epithelium & colorectal epithelium cancer (at protein level)
- expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon & peripheral blood leukocytes
Pathology
- does not interact with ERCC3 or repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells
- isoform 6 is expressed in colorectal epithelial cancer but below detection level in colonic epithelium
More general terms
- DNA-binding protein
- splicing factor; snRNP-associated protein
- transcriptional silencer (transcriptional repressor)