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

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

Author information

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
Division of Newborn Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany.
Contributed equally


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.

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