CUGBP1
CELF1 | |||
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Gene ontology | |||
Molecular function | |||
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Biological process | |||
Sources:Amigo / QuickGO |
View/Edit Human |
CUG triplet repeat, RNA binding protein 1, also known as CUGBP1, is a protein which in humans is encoded by the CUGBP1 gene.[3][4][5]
Function
Members of the
mRNA degradation factor
It is estimated that 5 to 8% of human
Evidence for CUGBP1 acting as a RNA degradation factor came first from the Xenopus model. Xenopus CUGBP1 (xCUGBP1, formerly known as EDEN-BP) was identified in 1998[8] for its ability to bind specifically to a GU-rich element (Embryonic deadenylation element EDEN) located in the 3'UTRs of some mRNAs that are rapidly deadenylated and translationally repressed after fertilization in early development. Because deadenylation is often the rate limiting step of mRNA degradation the enhancement of deadenylation increases mRNA turnover.[9]
Human CUGBP1 (hCUGBP1) had been previously identified by Timchenko and colleagues[4] for its ability to bind to CUG repeats located in the DMPK 3'UTR. A large amount of work has since described the role of hCUGBP1 on control of alternative splicing and will not be discussed here.[10] The demonstration that hCUGBP1 is involved in the control of mRNA deadenylation and instability like xCUGBP1 came next. In mammalian cell extract as well as in xenopus egg extracts, depletion and rescue experiments showed that specific binding of CUGBP1 to the 3'UTR of mRNA is required for the targeted specific deadenylation to occur.[11] In rescue experiments in xenopus egg extracts, the recombinant human protein can replace the xenopus one making them functional homolog.[12] Furthermore, the Poly(A) ribonuclease PARN was shown to interact with CUGBP1.[13] In human cells, tethering of hCUGBP1 to a mRNA decreases its steadystate suggesting the destabilization of the mRNA.[14] The first human mRNA reported to be targeted to rapid deadenylation and degradation by CUGBP1 is the oncogene c-jun. Years ago, it was shown that the class III ARE (devoid of any AUUUA motif) of the human c-jun oncogene directed rapid deadenylation and degradation to a reporter mRNA.[15] Both xCUGBP1 and hCUGBP1 were shown to specifically bind to c-jun ARE.[11] The binding of CUGBP1 to the 3'UTR of mRNAs bearing GU-rich element would target these mRNAs for rapid deadenylation by PARN and subsequent degradation. This was recently demonstrated by siRNA-mediated knockdown of hCUGBP1 that led to stabilization of a reporter RNA bearing the c-jun UG -rich ARE.[16]
UGU(G/A) tetranucleotides are key determinants of the binding site for xCUGBP1. A
Immunoprecipitation of the CUGBP1 containing complexes has led Graindorge et al. to propose a 15 nt motif as a key determinant of CUGBP1 binding.[18] Such a motif is found in a number of unstable mRNAs in human cells[16] suggesting that they are degraded by a CUGBP1 deadenylation dependent pathway.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000149187 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: CUGBP1 CUG triplet repeat, RNA binding protein 1".
- ^ PMID 8948631.
- PMID 9371827.
- PMID 11125104.
- PMID 18042543.
- PMID 9427761.
- S2CID 21227254.
- PMID 17823658.
- ^ PMID 11707455.
- S2CID 32334637.
- PMID 16601207.
- PMID 16843434.
- PMID 8657122.
- ^ PMID 18243120.
- PMID 16938098.
- PMID 18267972.
External links
- Human CELF1 genome location and CELF1 gene details page in the UCSC Genome Browser.
Further reading
- Timchenko LT, Timchenko NA, Caskey CT, Roberts R (1996). "Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy". Hum. Mol. Genet. 5 (1): 115–21. PMID 8789448.
- Bhagwati S, Ghatpande A, Leung B (1996). "Identification of two nuclear proteins which bind to RNA CUG repeats: significance for myotonic dystrophy". Biochem. Biophys. Res. Commun. 228 (1): 55–62. PMID 8912635.
- Timchenko LT, Miller JW, Timchenko NA, et al. (1997). "Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy". Nucleic Acids Res. 24 (22): 4407–14. PMID 8948631.
- Roberts R, Timchenko NA, Miller JW, et al. (1998). "Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice". Proc. Natl. Acad. Sci. U.S.A. 94 (24): 13221–6. PMID 9371827.
- Michalowski S, Miller JW, Urbinati CR, et al. (1999). "Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein". Nucleic Acids Res. 27 (17): 3534–42. PMID 10446244.
- Timchenko NA, Welm AL, Lu X, Timchenko LT (1999). "CUG repeat binding protein (CUGBP1) interacts with the 5' region of C/EBPbeta mRNA and regulates translation of C/EBPbeta isoforms". Nucleic Acids Res. 27 (22): 4517–25. PMID 10536163.
- Good PJ, Chen Q, Warner SJ, Herring DC (2000). "A family of human RNA-binding proteins related to the Drosophila Bruno translational regulator". J. Biol. Chem. 275 (37): 28583–92. PMID 10893231.
- Timchenko NA, Cai ZJ, Welm AL, et al. (2001). "RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1". J. Biol. Chem. 276 (11): 7820–6. PMID 11124939.
- Ladd AN, Charlet N, Cooper TA (2001). "The CELF Family of RNA Binding Proteins Is Implicated in Cell-Specific and Developmentally Regulated Alternative Splicing". Mol. Cell. Biol. 21 (4): 1285–96. PMID 11158314.
- Timchenko NA, Iakova P, Cai ZJ, et al. (2001). "Molecular Basis for Impaired Muscle Differentiation in Myotonic Dystrophy". Mol. Cell. Biol. 21 (20): 6927–38. PMID 11564876.
- Takahashi N, Sasagawa N, Usuki F, et al. (2002). "Coexpression of the CUG-binding protein reduces DM protein kinase expression in COS cells". J. Biochem. 130 (5): 581–7. PMID 11686919.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Paillard L, Legagneux V, Beverley Osborne H (2003). "A functional deadenylation assay identifies human CUG-BP as a deadenylation factor". Biol. Cell. 95 (2): 107–13. S2CID 32334637.
- Ebralidze A, Wang Y, Petkova V, et al. (2004). "RNA leaching of transcription factors disrupts transcription in myotonic dystrophy". Science. 303 (5656): 383–7. S2CID 30836956.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. PMID 14702039.
- Hillman RT, Green RE, Brenner SE (2005). "An unappreciated role for RNA surveillance". Genome Biol. 5 (2): R8. PMID 14759258.
- Baldwin BR, Timchenko NA, Zahnow CA (2004). "Epidermal Growth Factor Receptor Stimulation Activates the RNA Binding Protein CUG-BP1 and Increases Expression of C/EBPβ-LIP in Mammary Epithelial Cells". Mol. Cell. Biol. 24 (9): 3682–91. PMID 15082764.
- Watanabe T, Takagi A, Sasagawa N, et al. (2004). "Altered expression of CUG binding protein 1 mRNA in myotonic dystrophy 1: possible RNA-RNA interaction". Neurosci. Res. 49 (1): 47–54. S2CID 32863977.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. PMID 15489334.
- Dansithong W, Paul S, Comai L, Reddy S (2005). "MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1". J. Biol. Chem. 280 (7): 5773–80. PMID 15546872.