Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt.
Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt.
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DOI：
10.1038/nsmb.3140
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发表时间：
2016-01
影响因子：
16.8
通讯作者：
Patel DJ
中科院分区：
文献类型：
--
作者：
Murn J;Teplova M;Zarnack K;Shi Y;Patel DJ
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, ZnF–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.
