Recognition of distinct RNA motifs by the clustered CCCH zinc fingers of neuronal protein Unkempt View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-01

AUTHORS

Jernej Murn, Marianna Teplova, Kathi Zarnack, Yang Shi, Dinshaw J Patel

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. More... »

PAGES

16-23

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nsmb.3140

DOI

http://dx.doi.org/10.1038/nsmb.3140

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016177535

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26641712


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52 schema:description 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.
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