4b8t
From Proteopedia
RNA BINDING PROTEIN Solution structure of the third KH domain of KSRP in complex with the G-rich target sequence.
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 PubMedLet-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. Loading citation details.. Citations No citations found References
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