4b8t Citations

Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis.

OpenAccess logo Nat Struct Mol Biol 19 1282-6 (2012)
Related entries: 2hh2, 2hh3

Cited: 35 times
EuropePMC logo PMID: 23142982

Abstract

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.

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Reviews citing this publication (10)

  1. KH-RNA interactions: back in the groove. Nicastro G, Taylor IA, Ramos A. Curr Opin Struct Biol 30 63-70 (2015)
  2. The many faces of Dicer: the complexity of the mechanisms regulating Dicer gene expression and enzyme activities. Kurzynska-Kokorniak A, Koralewska N, Pokornowska M, Urbanowicz A, Tworak A, Mickiewicz A, Figlerowicz M. Nucleic Acids Res 43 4365-4380 (2015)
  3. KSRP controls pleiotropic cellular functions. Gherzi R, Chen CY, Ramos A, Briata P. Semin Cell Dev Biol 34 2-8 (2014)
  4. Post-translational Control of RNA-Binding Proteins and Disease-Related Dysregulation. Velázquez-Cruz A, Baños-Jaime B, Díaz-Quintana A, De la Rosa MA, Díaz-Moreno I. Front Mol Biosci 8 658852 (2021)
  5. Terminal loop-mediated regulation of miRNA biogenesis: selectivity and mechanisms. Castilla-Llorente V, Nicastro G, Ramos A. Biochem Soc Trans 41 861-865 (2013)
  6. Integrated structural biology to unravel molecular mechanisms of protein-RNA recognition. Schlundt A, Tants JN, Sattler M. Methods 118-119 119-136 (2017)
  7. Deciphering the protein-RNA recognition code: combining large-scale quantitative methods with structural biology. Hennig J, Sattler M. Bioessays 37 899-908 (2015)
  8. NMR solution structure determination of large RNA-protein complexes. Yadav DK, Lukavsky PJ. Prog Nucl Magn Reson Spectrosc 97 57-81 (2016)
  9. Joining the dots - protein-RNA interactions mediating local mRNA translation in neurons. Gallagher C, Ramos A. FEBS Lett 592 2932-2947 (2018)
  10. The Role of KH-Type Splicing Regulatory Protein (KSRP) for Immune Functions and Tumorigenesis. Palzer KA, Bolduan V, Käfer R, Kleinert H, Bros M, Pautz A. Cells 11 1482 (2022)

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