6G70

Structure of murine Prpf39

Summary for 6G70

• Entry DOI: 10.2210/pdb6g70/pdb
• Descriptor: Pre-mRNA-processing factor 39 (1 entity in total)
• Functional Keywords: u1snrnp, hat repeat protein, splicing
• Biological source: Mus musculus (House Mouse)
• Total number of polymer chains: 2
• Total formula weight: 156875.33

Authors

De Bortoli, F.D.,Loll, B.,Wahl, M.,Heyd, F. (deposition date: 2018-04-04, release date: 2019-04-03, Last modification date: 2024-05-08)

Primary citation

De Bortoli, F.,Neumann, A.,Kotte, A.,Timmermann, B.,Schuler, T.,Wahl, M.C.,Loll, B.,Heyd, F.
Increased versatility despite reduced molecular complexity: evolution, structure and function of metazoan splicing factor PRPF39.
Nucleic Acids Res., 47:5867-5879, 2019

PubMed Abstract: In the yeast U1 snRNP the Prp39/Prp42 heterodimer is essential for early steps of spliceosome assembly. In metazoans no Prp42 ortholog exists, raising the question how the heterodimer is functionally substituted. Here we present the crystal structure of murine PRPF39, which forms a homodimer. Structure-guided point mutations disrupt dimer formation and inhibit splicing, manifesting the homodimer as functional unit. PRPF39 expression is controlled by NMD-inducing alternative splicing in mice and human, suggesting a role in adapting splicing efficiency to cell type specific requirements. A phylogenetic analysis reveals coevolution of shortened U1 snRNA and the absence of Prp42, which correlates with overall splicing complexity in different fungi. While current models correlate the diversity of spliceosomal proteins with splicing complexity, our study highlights a contrary case. We find that organisms with higher splicing complexity have substituted the Prp39/Prp42 heterodimer with a PRPF39 homodimer.

PubMed: 30949712
DOI: 10.1093/nar/gkz243

Experimental method

X-RAY DIFFRACTION (3.3 Å)