2my8

Structural highlights

Function

[CELF2_HUMAN] RNA-binding protein implicated in the regulation of several post-transcriptional events. Involved in pre-mRNA alternative splicing, mRNA translation and stability. Mediates exon inclusion and/or exclusion in pre-mRNA that are subject to tissue-specific and 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 the repressive effect of PTB. Acts as both an activator and repressor of a pair of coregulated exons: promotes inclusion of the smooth muscle (SM) exon but exclusion of the non-muscle (NM) exon in actinin pre-mRNAs. Promotes inclusion of exonS 21 and exclusion of exon 5 of the NMDA receptor R1 pre-mRNA. Involved in the apoB RNA editing activity. Increases COX2 mRNA stability and inhibits COX2 mRNA translation in epithelial cells after radiation injury (By similarity). Modulates the cellular apoptosis program by regulating COX2-mediated prostaglandin E2 (PGE2) expression (By similarity). Binds to (CUG)n triplet repeats in the 3'-UTR of transcripts such as DMPK. Binds to the muscle-specific splicing enhancer (MSE) intronic sites flanking the TNNT2 alternative exon 5. Binds preferentially to UG-rich sequences, in particular UG repeat and 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 (By similarity). Binds to an intronic RNA element responsible for the silencing of exon 21 splicing (By similarity). Binds to (CUG)n repeats (By similarity).^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Anant S, Henderson JO, Mukhopadhyay D, Navaratnam N, Kennedy S, Min J, Davidson NO. Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. J Biol Chem. 2001 Dec 14;276(50):47338-51. Epub 2001 Sep 27. PMID:11577082 doi:http://dx.doi.org/10.1074/jbc.M104911200
2. ↑ Ladd AN, Charlet N, Cooper TA. The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing. Mol Cell Biol. 2001 Feb;21(4):1285-96. PMID:11158314 doi:10.1128/MCB.21.4.1285-1296.2001
3. ↑ Charlet-B N, Logan P, Singh G, Cooper TA. Dynamic antagonism between ETR-3 and PTB regulates cell type-specific alternative splicing. Mol Cell. 2002 Mar;9(3):649-58. PMID:11931771
4. ↑ Gromak N, Matlin AJ, Cooper TA, Smith CW. Antagonistic regulation of alpha-actinin alternative splicing by CELF proteins and polypyrimidine tract binding protein. RNA. 2003 Apr;9(4):443-56. PMID:12649496
5. ↑ Singh G, Charlet-B N, Han J, Cooper TA. ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in vivo. Nucleic Acids Res. 2004 Feb 18;32(3):1232-41. Print 2004. PMID:14973222 doi:http://dx.doi.org/10.1093/nar/gkh275
6. ↑ Faustino NA, Cooper TA. Identification of putative new splicing targets for ETR-3 using sequences identified by systematic evolution of ligands by exponential enrichment. Mol Cell Biol. 2005 Feb;25(3):879-87. PMID:15657417 doi:http://dx.doi.org/10.1128/MCB.25.3.879-887.2005
7. ↑ Han J, Cooper TA. Identification of CELF splicing activation and repression domains in vivo. Nucleic Acids Res. 2005 May 13;33(9):2769-80. Print 2005. PMID:15894795 doi:http://dx.doi.org/10.1093/nar/gki561
8. ↑ Bhatt H, Ganguly AK, Sharma S, Kushwaha GS, Firoz Khan M, Sen S, Bhavesh NS. Structure of an Unfolding Intermediate of an RRM Domain of ETR-3 Reveals Its Native-like Fold. Biophys J. 2019 Dec 6. pii: S0006-3495(19)34350-4. doi:, 10.1016/j.bpj.2019.11.3392. PMID:31866002 doi:http://dx.doi.org/10.1016/j.bpj.2019.11.3392