6gc5 | pdb_00006gc5

Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM

spinqualitylabelsall models 6gc5, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gc5 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: ELAVL1, HUR (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [ELAV1_HUMAN] Involved in 3'-UTR ARE-mediated MYC stabilization. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, HUR binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro. Publication Abstract from PubMed Human antigen R (HuR) is a key regulator of cellular mRNAs containing adenylate/uridylate-rich elements (AU-rich elements; AREs). These are a major class of cis elements within 3' untranslated regions, targeting these mRNAs for rapid degradation. HuR contains three RNA recognition motifs (RRMs): a tandem RRM1 and 2, followed by a flexible linker and a C-terminal RRM3. While RRM1 and 2 are structurally characterized, little is known about RRM3. Here we present a 1.9-A-resolution crystal structure of RRM3 bound to different ARE motifs. This structure together with biophysical methods and cell-culture assays revealed the mechanism of RRM3 ARE recognition and dimerization. While multiple RNA motifs can be bound, recognition of the canonical AUUUA pentameric motif is possible by binding to two registers. Additionally, RRM3 forms homodimers to increase its RNA binding affinity. Finally, although HuR stabilizes ARE-containing RNAs, we found that RRM3 counteracts this effect, as shown in a cell-based ARE reporter assay and by qPCR with native HuR mRNA targets containing multiple AUUUA motifs, possibly by competing with RRM12. Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM.,Ripin N, Boudet J, Duszczyk MM, Hinniger A, Faller M, Krepl M, Gadi A, Schneider RJ, Sponer J, Meisner-Kober NC, Allain FH Proc Natl Acad Sci U S A. 2019 Feb 4. pii: 1808696116. doi:, 10.1073/pnas.1808696116. PMID:30718402 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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