CUG-BP- & ETR-3-like factor 2 (CELF-2, Bruno-like protein 3, RNA-binding protein BRUNOL-3, CUG triplet repeat RNA-binding protein 2, CUG-BP2, ELAV-type RNA-binding protein 3, ETR-3, neuroblastoma apoptosis-related RNA-binding protein, hNAPOR, CUGBP2, BRUNOL3, CELF2, ETR3, NAPOR)
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Function
- RNA-binding protein
- role in regulation of several post-transcriptional events
- role in pre-mRNA alternative splicing, mRNA translation & stability
- mediates exon inclusion &/or exclusion in pre-mRNA subject to tissue-specific & developmentally regulated alternative splicing
- specifically activates exon 5 inclusion of TNNT2 in embryonic, but not adult, skeletal muscle
- activates TNNT2 exon 5 inclusion by antagonizing repressive effect of PTB
- role as both an activator & repressor of a pair of coregulated exons:
- promotes inclusion of exon 21 & exclusion of exon 5 of NMDA receptor R1 pre-mRNA
- role in apoB RNA editing activity
- increases COX2 mRNA stability & inhibits COX2 mRNA translation in epithelial cells after radiation injury
- modulates cellular apoptosis by regulating COX2-mediated prostaglandin E2 (PGE2) expression
- binds to (CUG)n triplet repeats in 3'-UTR of transcripts such as DMPK
- binds to muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5
- binds preferentially to UG-rich sequences, in particular UG repeat & UGUU motifs
- binds to apoB mRNA, specifically to AU-rich sequences located immediatly upstream of the edited cytidine
- binds AU-rich sequences in the 3'-UTR of COX2 mRNA
- binds to intronic RNA element responsible for the silencing of exon splicing
- found in a complex with APOBEC1 & ACF
Structure
- belongs to the CELF/BRUNOL family
- contains 3 RRM domains (RNA recognition motif)
Compartment
- nucleus, cytoplasm
- accumulates in cytoplasm after ionizing radiation
- colocalizes with APOBEC1 & ACF
- RNA-binding activity is detected in both nuclear & cytoplasmic compartments
Alternative splicing
named isoforms=5
Expression
- expressed in frontal cortex
- isoform 1 isexpressed in brain & lung
- isoform 2 is expressed in heart, brain, placenta, lung, liver, kidney, skeletal muscle & pancreas
- isoform 4 is expressed in heart, lung, skeletal muscle, kidney & pancreas
- isoform 1 is expressed in fetal brain
- isoform 2 is expressed in fetal heart, brain, thymus, lung, liver, skeletal muscle, kidney & spleen
- isoform 4 is expressed in fetal heart, brain, thymus, lung & skeletal muscle