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

Journal Article · · Nature Structural & Molecular Biology
DOI:https://doi.org/10.1038/nsmb.3140· OSTI ID:1234759
 [1];  [2];  [3];  [1];  [2]
  1. Harvard Medical School, Boston, MA (United States); Boston Children's Hospital, Boston, MA (United States)
  2. Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
  3. Goethe Univ. Frankfurt (Germany)
+ Show Author Affiliations

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. Furthermore, 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
U.S. National Inst. of Health; Memorial Sloan Kettering Cancer Center
Grant/Contract Number:
MH096066; GM104962; P3O CA008748
OSTI ID:
1234759
Journal Information:
Nature Structural & Molecular Biology, Vol. 23, Issue 1; ISSN 1545-9993
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 17 works
Citation information provided by
Web of Science

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Cited By (4)

Correction to: Methylation of ZNF331 is an independent prognostic marker of colorectal cancer and promotes colorectal cancer growth journal March 2018
Human m 6 A writers: Two subunits, 2 roles journal February 2017
Structure of the zinc-finger antiviral protein in complex with RNA reveals a mechanism for selective targeting of CG-rich viral sequences journal November 2019
An engineered RNA binding protein with improved splicing regulation journal January 2018

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59 BASIC BIOLOGICAL SCIENCES
Proteins
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X-ray crystallography