Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt Journal Article
| Authors: | Murn, J.; Teplova, M.; Zarnack, K.; Shi, Y.; Patel, D. J. |
| Article Title: | Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt |
| Abstract: | 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. © 2016 Nature America, Inc. |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 23 |
| Issue: | 1 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2016-01-01 |
| Start Page: | 16 |
| End Page: | 23 |
| Language: | English |
| DOI: | 10.1038/nsmb.3140 |
| PROVIDER: | scopus |
| PMCID: | PMC4703518 |
| PUBMED: | 26641712 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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