Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt
- Harvard Medical School, Boston, MA (United States); Boston Children's Hospital, Boston, MA (United States)
- Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
- Goethe Univ. Frankfurt (Germany)
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
Web of Science
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 |
Similar Records
Distinctive structural basis for DNA recognition by the fission yeast Zn2Cys6 transcription factor Pho7 and its role in phosphate homeostasis
Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants