7VKI

ESRP1 qRRM2 in complex with 12mer-RNA

Summary for 7VKI

• Entry DOI: 10.2210/pdb7vki/pdb
• Descriptor: Epithelial splicing regulatory protein 1, RNA (12-mer) (3 entities in total)
• Functional Keywords: qrrm domain, rna binding, circrna, complex, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 17151.49

Authors

Wu, B.X.,Patel, D.J. (deposition date: 2021-09-30, release date: 2022-10-05, Last modification date: 2024-11-13)

Primary citation

Liu, D.,Dredge, B.K.,Bert, A.G.,Pillman, K.A.,Toubia, J.,Guo, W.,Dyakov, B.J.A.,Migault, M.M.,Conn, V.M.,Conn, S.J.,Gregory, P.A.,Gingras, A.C.,Patel, D.,Wu, B.,Goodall, G.J.
ESRP1 controls biogenesis and function of a large abundant multiexon circRNA.
Nucleic Acids Res., 2023

PubMed Abstract: While the majority of circRNAs are formed from infrequent back-splicing of exons from protein coding genes, some can be produced at quite high level and in a regulated manner. We describe the regulation, biogenesis and function of circDOCK1(2-27), a large, abundant circular RNA that is highly regulated during epithelial-mesenchymal transition (EMT) and whose formation depends on the epithelial splicing regulator ESRP1. CircDOCK1(2-27) synthesis in epithelial cells represses cell motility both by diverting transcripts from DOCK1 mRNA production to circRNA formation and by direct inhibition of migration by the circRNA. HITS-CLIP analysis and CRISPR-mediated deletions indicate ESRP1 controls circDOCK1(2-27) biosynthesis by binding a GGU-containing repeat region in intron 1 and detaining its splicing until Pol II completes its 157 kb journey to exon 27. Proximity-dependent biotinylation (BioID) assay suggests ESRP1 may modify the RNP landscape of intron 1 in a way that disfavours communication of exon 1 with exon 2, rather than physically bridging exon 2 to exon 27. The X-ray crystal structure of RNA-bound ESRP1 qRRM2 domain reveals it binds to GGU motifs, with the guanines embedded in clamp-like aromatic pockets in the protein.

PubMed: 38015468
DOI: 10.1093/nar/gkad1138

Experimental method

X-RAY DIFFRACTION (1.65 Å)