Structural highlights
Function
[UNK_MOUSE] Sequence-specific RNA-binding protein which plays an important role in the establishment and maintenance of the early morphology of cortical neurons during embryonic development. Acts as a translation repressor and controls a translationally regulated cell morphology program to ensure proper structuring of the nervous system. Translational control depends on recognition of its binding element within target mRNAs which consists of a mandatory UAG trimer upstream of a U/A-rich motif. Associated with polysomes (PubMed:25737280).[1]
Publication Abstract from PubMed
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.
Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt.,Murn J, Teplova M, Zarnack K, Shi Y, Patel DJ Nat Struct Mol Biol. 2015 Dec 7. doi: 10.1038/nsmb.3140. PMID:26641712[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murn J, Zarnack K, Yang YJ, Durak O, Murphy EA, Cheloufi S, Gonzalez DM, Teplova M, Curk T, Zuber J, Patel DJ, Ule J, Luscombe NM, Tsai LH, Walsh CA, Shi Y. Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev. 2015 Mar 1;29(5):501-12. doi: 10.1101/gad.258483.115. PMID:25737280 doi:http://dx.doi.org/10.1101/gad.258483.115
- ↑ Murn J, Teplova M, Zarnack K, Shi Y, Patel DJ. Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt. Nat Struct Mol Biol. 2015 Dec 7. doi: 10.1038/nsmb.3140. PMID:26641712 doi:http://dx.doi.org/10.1038/nsmb.3140
