4YH8

Structure of yeast U2AF complex

Summary for 4YH8

• Entry DOI: 10.2210/pdb4yh8/pdb
• Descriptor: Splicing factor U2AF 23 kDa subunit, Splicing factor U2AF 59 kDa subunit, ZINC ION, ... (4 entities in total)
• Functional Keywords: splicing, rrm, zn-finger, 3' splice site
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 2
• Total formula weight: 33140.05

Authors

Yoshida, H.,Park, S.Y.,Urano, T.,Obayashi, E. (deposition date: 2015-02-27, release date: 2015-08-12, Last modification date: 2024-03-20)

Primary citation

Yoshida, H.,Park, S.Y.,Oda, T.,Akiyoshi, T.,Sato, M.,Shirouzu, M.,Tsuda, K.,Kuwasako, K.,Unzai, S.,Muto, Y.,Urano, T.,Obayashi, E.
A novel 3' splice site recognition by the two zinc fingers in the U2AF small subunit.
Genes Dev., 29:1649-1660, 2015

PubMed Abstract: The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3' splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the β sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein.

PubMed: 26215567
DOI: 10.1101/gad.267104.115

Experimental method

X-RAY DIFFRACTION (1.7 Å)