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The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding
Journal article   Open access   Peer reviewed

The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding

Caroline Rajiv, S RaElle Jackson, Simon Cocklin, Elan Z Eisenmesser and Tara L Davis
Biochemical journal, v 474(21), pp 3689-3704
25 Oct 2017
DOI: https://doi.org/10.1042/BCJ20170366
PMID: 28935721
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc5682932View
Accepted (AM),  Open

Abstract

Calorimetry Circular Dichroism Cloning, Molecular Intrinsically Disordered Proteins - metabolism Peptidylprolyl Isomerase - genetics Peptidylprolyl Isomerase - metabolism Protein Binding Ribonucleoprotein, U4-U6 Small Nuclear - genetics Ribonucleoprotein, U4-U6 Small Nuclear - metabolism RNA Splicing Spliceosomes - metabolism Surface Plasmon Resonance Ultracentrifugation
Pre-mRNA splicing is a dynamic, multistep process that is catalyzed by the RNA (ribonucleic acid)-protein complex called the spliceosome. The spliceosome contains a core set of RNAs and proteins that are conserved in all organisms that perform splicing. In higher organisms, peptidyl-prolyl isomerase H (PPIH) directly interacts with the core protein pre-mRNA processing factor 4 (PRPF4) and both integrate into the pre-catalytic spliceosome as part of the tri-snRNP (small nuclear RNA-protein complex) subcomplex. As a first step to understand the protein interactions that dictate PPIH and PRPF4 function, we expressed and purified soluble forms of each protein and formed a complex between them. We found two sites of interaction between PPIH and the N-terminus of PRPF4, an unexpected result. The N-terminus of PRPF4 is an intrinsically disordered region and does not adopt secondary structure in the presence of PPIH. In the absence of an atomic resolution structure, we used mutational analysis to identify point mutations that uncouple these two binding sites and find that mutations in both sites are necessary to break up the complex. A discussion of how this bipartite interaction between PPIH and PRPF4 may modulate spliceosomal function is included.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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