2n8l

Structural highlights

Function

IF2B1_CHICK RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.^{[1] [2] [3] [4] [5] [6] [7]}

See Also

• Insulin-like growth factor 2 mRNA-binding protein

References

1. ↑ Zhang HL, Eom T, Oleynikov Y, Shenoy SM, Liebelt DA, Dictenberg JB, Singer RH, Bassell GJ. Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility. Neuron. 2001 Aug 2;31(2):261-75. PMID:11502257
2. ↑ Farina KL, Huttelmaier S, Musunuru K, Darnell R, Singer RH. Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment. J Cell Biol. 2003 Jan 6;160(1):77-87. Epub 2002 Dec 30. PMID:12507992 doi:http://dx.doi.org/10.1083/jcb.200206003
3. ↑ Oleynikov Y, Singer RH. Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization. Curr Biol. 2003 Feb 4;13(3):199-207. PMID:12573215
4. ↑ Huttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X, Bassell GJ, Condeelis J, Singer RH. Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1. Nature. 2005 Nov 24;438(7067):512-5. PMID:16306994 doi:nature04115
5. ↑ Stohr N, Kohn M, Lederer M, Glass M, Reinke C, Singer RH, Huttelmaier S. IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev. 2012 Jan 15;26(2):176-89. doi: 10.1101/gad.177642.111. PMID:22279049 doi:http://dx.doi.org/10.1101/gad.177642.111
6. ↑ Wachter K, Kohn M, Stohr N, Huttelmaier S. Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains. Biol Chem. 2013 Aug;394(8):1077-90. doi: 10.1515/hsz-2013-0111. PMID:23640942 doi:http://dx.doi.org/10.1515/hsz-2013-0111
7. ↑ Ross AF, Oleynikov Y, Kislauskis EH, Taneja KL, Singer RH. Characterization of a beta-actin mRNA zipcode-binding protein. Mol Cell Biol. 1997 Apr;17(4):2158-65. PMID:9121465