4jvy
From Proteopedia
Structure of the STAR (signal transduction and activation of RNA) domain of GLD-1 bound to RNA
Structural highlights
FunctionGLD1_CAEEL Germ line-specific tumor suppressor essential for oogenesis. Controls the spatial pattern of translation of multiple oogenesis specific mRNAs (e.g. yolk receptor rme-2) by repression of translation during early meiotic prophase (leptotene to pachytene) and then derepression of translation during diplotene/ diakinesis, following its degradation. Also functions to promote the male sexual fate in the hermaphrodite germline but not the male germline. Functions redundantly with gld-2 to promote the initiation of meiotic development and/or inhibit stem cell proliferation. Publication Abstract from PubMedMammalian Quaking (QKI) and its Caenorhabditis elegans homolog, GLD-1 (defective in germ line development), are evolutionarily conserved RNA-binding proteins, which post-transcriptionally regulate target genes essential for developmental processes and myelination. We present X-ray structures of the STAR (signal transduction and activation of RNA) domain, composed of Qua1, K homology (KH), and Qua2 motifs of QKI and GLD-1 bound to high-affinity in vivo RNA targets containing YUAAY RNA recognition elements (RREs). The KH and Qua2 motifs of the STAR domain synergize to specifically interact with bases and sugar-phosphate backbones of the bound RRE. Qua1-mediated homodimerization generates a scaffold that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in many QKI-targeted transcripts. Structure-guided mutations reduced QKI RNA-binding affinity in vitro and in vivo, and expression of QKI mutants in human embryonic kidney cells (HEK293) significantly decreased the abundance of QKI target mRNAs. Overall, our studies define principles underlying RNA target selection by STAR homodimers and provide insights into the post-transcriptional regulatory function of mammalian QKI proteins. Structure-function studies of STAR family Quaking proteins bound to their in vivo RNA target sites.,Teplova M, Hafner M, Teplov D, Essig K, Tuschl T, Patel DJ Genes Dev. 2013 Apr 15;27(8):928-40. doi: 10.1101/gad.216531.113. PMID:23630077[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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