Structural highlights
Function
[FUBP2_HUMAN] Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.[1] [2] [3]
Publication Abstract from PubMed
Let-7 is an important tumor-suppressive microRNA (miRNA) that acts as an on-off switch for cellular differentiation and regulates the expression of a set of human oncogenes. Binding of the human KSRP protein to let-7 miRNA precursors positively regulates their processing to mature let-7, thereby contributing to control of cell proliferation, apoptosis and differentiation. Here we analyze the molecular basis for KSRP-let-7 precursor selectivity and show how the third KH domain of the protein recognizes a G-rich sequence in the pre-let-7 terminal loop and dominates the interaction. The structure of the KH3-RNA complex explains the protein recognition of this noncanonical KH target sequence, and we demonstrate that the specificity of this binding is crucial for the functional interaction between the protein and the miRNA precursor.
Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis.,Nicastro G, Garcia-Mayoral MF, Hollingworth D, Kelly G, Martin SR, Briata P, Gherzi R, Ramos A Nat Struct Mol Biol. 2012 Nov 11. doi: 10.1038/nsmb.2427. PMID:23142982[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Min H, Turck CW, Nikolic JM, Black DL. A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer. Genes Dev. 1997 Apr 15;11(8):1023-36. PMID:9136930
- ↑ Davis-Smyth T, Duncan RC, Zheng T, Michelotti G, Levens D. The far upstream element-binding proteins comprise an ancient family of single-strand DNA-binding transactivators. J Biol Chem. 1996 Dec 6;271(49):31679-87. PMID:8940189
- ↑ Markovtsov V, Nikolic JM, Goldman JA, Turck CW, Chou MY, Black DL. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol Cell Biol. 2000 Oct;20(20):7463-79. PMID:11003644
- ↑ Nicastro G, Garcia-Mayoral MF, Hollingworth D, Kelly G, Martin SR, Briata P, Gherzi R, Ramos A. Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis. Nat Struct Mol Biol. 2012 Nov 11. doi: 10.1038/nsmb.2427. PMID:23142982 doi:http://dx.doi.org/10.1038/nsmb.2427
