Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt

Nat Struct Mol Biol. 2016 Jan;23(1):16-23. doi: 10.1038/nsmb.3140. Epub 2015 Dec 7.


Unkempt is an evolutionarily conserved RNA-binding protein that regulates translation of its target genes and is required for the establishment of the early bipolar neuronal morphology. Here we determined the X-ray crystal structure of mouse Unkempt and show that its six CCCH zinc fingers (ZnFs) form two compact clusters, ZnF1-3 and ZnF4-6, that recognize distinct trinucleotide RNA substrates. Both ZnF clusters adopt a similar overall topology and use distinct recognition principles to target specific RNA sequences. Structure-guided point mutations reduce the RNA binding affinity of Unkempt both in vitro and in vivo, ablate Unkempt's translational control and impair the ability of Unkempt to induce a bipolar cellular morphology. Our study unravels a new mode of RNA sequence recognition by clusters of CCCH ZnFs that is critical for post-transcriptional control of neuronal morphology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Crystallography, X-Ray
  • Mice
  • Models, Molecular
  • Nucleotide Motifs*
  • Protein Binding
  • Protein Conformation
  • RNA / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Zinc Fingers*


  • Carrier Proteins
  • RNA-Binding Proteins
  • unkempt protein, mouse
  • RNA

Associated data

  • PDB/5ELH
  • PDB/5ELK