6GC5

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

Summary for 6GC5

• Entry DOI: 10.2210/pdb6gc5/pdb
• Descriptor: ELAV-like protein 1, AU-rich RNA (3 entities in total)
• Functional Keywords: elav, hur, rrm3, dimer, rrm, rna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 8
• Total formula weight: 53205.23

Authors

Ripin, N.,Allain, F.H. (deposition date: 2018-04-17, release date: 2019-01-30, Last modification date: 2024-01-17)

Primary citation

Ripin, N.,Boudet, J.,Duszczyk, M.M.,Hinniger, A.,Faller, M.,Krepl, M.,Gadi, A.,Schneider, R.J.,Sponer, J.,Meisner-Kober, N.C.,Allain, F.H.
Molecular basis for AU-rich element recognition and dimerization by the HuR C-terminal RRM.
Proc. Natl. Acad. Sci. U.S.A., 116:2935-2944, 2019

PubMed Abstract: 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 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-Å-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.

PubMed: 30718402
DOI: 10.1073/pnas.1808696116

Experimental method

X-RAY DIFFRACTION (1.9 Å)