| Structural highlights
Function
[IF2B1_HUMAN] RNA-binding factor that affects mRNA nuclear export, localization, stability and translation. Component of the CRD-mediated complex that promotes MYC mRNA stabilization. Regulates mRNA stability during the integrated cellular stress response (ISR) in stress granules (SGs). Stabilizes the BTRC/FBW1A mRNA from degradation by disrupting miRNA-dependent interaction with AGO2. Identified in a HCV IRES-mediated translation complex, that enhances translation at the Hepatitis C virus (HCV) RNA-replicon via the internal ribosome entry site (IRES), but does not affect 5'cap-dependent translation. Acts as a HIV-1 retrovirus restriction factor that reduces HIV-1 assembly by inhibiting viral RNA packaging, assembly and processing of HIV-1 GAG protein on cellular membranes. Binds to mRNAs in stress granules (SGs). Binds to the stem-loop IV of the 5'-UTR and to the variable region and the poly(U-C) motif of the 3'-UTR of the HCV RNA-replicon. Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNA and regulates its subcellular localization and translation. Binds both to the coding region mRNA stability determinant (CRD) and to AU-rich sequences in the 3'-UTR of the MYC and CD44 mRNAs and stabilizes these mRNAs. Binds to the fourth and fifth exons of the oncofetal H19 and neuron-specific TAU mRNAs and regulates their localizations. Binds to the adenine-rich autoregulatory sequence (ARS) 5'-UTR of the PABPC1 mRNA and is involved in its translational repression. The RNA-binding activity to ARS is stimulated by PABPC1. Binds to the coding sequence region of BTRC/FBW1A mRNA and mediates stabilization of BTRC/FBW1A and MYC mRNAs in response to beta-catenin signaling. Binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerisation. Also involved in growth or survival of lung-cancer cells. Protects the MYC and MDR-1 mRNAs from cleavage by a endoribonuclease, thus prolonging their stabilities (By similarity). Binds to the 3'-UTR axonal localization signal (ALS) of TAU mRNA (By similarity). Binds to a conserved 54-nucleotide element in the 3'-UTR of the beta actin mRNA known as the 'zipcode' (By similarity). Promotes translocation of the beta-actin mRNA to dendrites (By similarity). May act as a regulator of mRNA transport to activated synapses in response to synaptic activity (By similarity).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ZBP1 (zipcode-binding protein 1) was originally discovered as a trans-acting factor for the "zipcode" in the 3' untranslated region (UTR) of the beta-actin mRNA that is important for its localization and translational regulation. Subsequently, ZBP1 has been found to be a multifunctional regulator of RNA metabolism that controls aspects of localization, stability, and translation for many mRNAs. To reveal how ZBP1 recognizes its RNA targets, we biochemically characterized the interaction between ZBP1 and the beta-actin zipcode. The third and fourth KH (hnRNP K homology) domains of ZBP1 specifically recognize a bipartite RNA element located within the first 28 nucleotides of the zipcode. The spacing between the RNA sequences is consistent with the structure of IMP1 KH34, the human ortholog of ZBP1, that we solved by X-ray crystallography. The tandem KH domains are arranged in an intramolecular anti-parallel pseudodimer conformation with the canonical RNA-binding surfaces at opposite ends of the molecule. This orientation of the KH domains requires that the RNA backbone must undergo an approximately 180 degrees change in direction in order for both KH domains to contact the RNA simultaneously. The RNA looping induced by ZBP1 binding provides a mechanism for specific recognition and may facilitate the assembly of post-transcriptional regulatory complexes by remodeling the bound transcript.
ZBP1 recognition of beta-actin zipcode induces RNA looping.,Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952[16]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nielsen J, Christiansen J, Lykke-Andersen J, Johnsen AH, Wewer UM, Nielsen FC. A family of insulin-like growth factor II mRNA-binding proteins represses translation in late development. Mol Cell Biol. 1999 Feb;19(2):1262-70. PMID:9891060
- ↑ Patel GP, Ma S, Bag J. The autoregulatory translational control element of poly(A)-binding protein mRNA forms a heteromeric ribonucleoprotein complex. Nucleic Acids Res. 2005 Dec 14;33(22):7074-89. Print 2005. PMID:16356927 doi:33/22/7074
- ↑ Prokipcak RD, Herrick DJ, Ross J. Purification and properties of a protein that binds to the C-terminal coding region of human c-myc mRNA. J Biol Chem. 1994 Mar 25;269(12):9261-9. PMID:8132663
- ↑ Runge S, Nielsen FC, Nielsen J, Lykke-Andersen J, Wewer UM, Christiansen J. H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein. J Biol Chem. 2000 Sep 22;275(38):29562-9. PMID:10875929 doi:10.1074/jbc.M001156200
- ↑ Lemm I, Ross J. Regulation of c-myc mRNA decay by translational pausing in a coding region instability determinant. Mol Cell Biol. 2002 Jun;22(12):3959-69. PMID:12024010
- ↑ Vikesaa J, Hansen TV, Jonson L, Borup R, Wewer UM, Christiansen J, Nielsen FC. RNA-binding IMPs promote cell adhesion and invadopodia formation. EMBO J. 2006 Apr 5;25(7):1456-68. Epub 2006 Mar 16. PMID:16541107 doi:7601039
- ↑ Stohr N, Lederer M, Reinke C, Meyer S, Hatzfeld M, Singer RH, Huttelmaier S. ZBP1 regulates mRNA stability during cellular stress. J Cell Biol. 2006 Nov 20;175(4):527-34. Epub 2006 Nov 13. PMID:17101699 doi:10.1083/jcb.200608071
- ↑ Noubissi FK, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, Minamoto T, Ross J, Fuchs SY, Spiegelman VS. CRD-BP mediates stabilization of betaTrCP1 and c-myc mRNA in response to beta-catenin signalling. Nature. 2006 Jun 15;441(7095):898-901. PMID:16778892 doi:nature04839
- ↑ Kato T, Hayama S, Yamabuki T, Ishikawa N, Miyamoto M, Ito T, Tsuchiya E, Kondo S, Nakamura Y, Daigo Y. Increased expression of insulin-like growth factor-II messenger RNA-binding protein 1 is associated with tumor progression in patients with lung cancer. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):434-42. PMID:17255263 doi:13/2/434
- ↑ Pan F, Huttelmaier S, Singer RH, Gu W. ZBP2 facilitates binding of ZBP1 to beta-actin mRNA during transcription. Mol Cell Biol. 2007 Dec;27(23):8340-51. Epub 2007 Sep 24. PMID:17893325 doi:10.1128/MCB.00972-07
- ↑ Zhou Y, Rong L, Lu J, Pan Q, Liang C. Insulin-like growth factor II mRNA binding protein 1 associates with Gag protein of human immunodeficiency virus type 1, and its overexpression affects virus assembly. J Virol. 2008 Jun;82(12):5683-92. doi: 10.1128/JVI.00189-08. Epub 2008 Apr 2. PMID:18385235 doi:10.1128/JVI.00189-08
- ↑ Elcheva I, Goswami S, Noubissi FK, Spiegelman VS. CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation. Mol Cell. 2009 Jul 31;35(2):240-6. doi: 10.1016/j.molcel.2009.06.007. PMID:19647520 doi:10.1016/j.molcel.2009.06.007
- ↑ Weidensdorfer D, Stohr N, Baude A, Lederer M, Kohn M, Schierhorn A, Buchmeier S, Wahle E, Huttelmaier S. Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs. RNA. 2009 Jan;15(1):104-15. doi: 10.1261/rna.1175909. Epub 2008 Nov 24. PMID:19029303 doi:10.1261/rna.1175909
- ↑ Weinlich S, Huttelmaier S, Schierhorn A, Behrens SE, Ostareck-Lederer A, Ostareck DH. IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3'UTR. RNA. 2009 Aug;15(8):1528-42. doi: 10.1261/rna.1578409. Epub 2009 Jun 18. PMID:19541769 doi:10.1261/rna.1578409
- ↑ Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH. ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952 doi:24/2/148
- ↑ Chao JA, Patskovsky Y, Patel V, Levy M, Almo SC, Singer RH. ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. 2010 Jan 15;24(2):148-58. PMID:20080952 doi:24/2/148
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