title: Cooperative structure of the heterotrimeric pre-mRNA retention and splicing complex.
abstract: The precursor mRNA (pre-mRNA) retention and splicing (RES) complex is a spliceosomal complex that is present in yeast and humans and is important for RNA splicing and retention of unspliced pre-mRNA. Here, we present the solution NMR structure of the RES core complex from Saccharomyces cerevisiae. Complex formation leads to an intricate folding of three components-Snu17p, Bud13p and Pml1p-that stabilizes the RNA-recognition motif (RRM) fold of Snu17p and increases binding affinity in tertiary interactions between the components by more than 100-fold compared to that in binary interactions. RES interacts with pre-mRNA within the spliceosome, and through the assembly of the RES core complex RNA binding efficiency is increased. The three-dimensional structure of the RES core complex highlights the importance of cooperative folding and binding in the functional organization of the spliceosome.
authors.affiliation: Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wysoczański
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Schneider
authors.affiliation: Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: ShengQi
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Munari
authors.affiliation: 1] Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. [2].
authors.forename: Simon
authors.identifier: 000000019143766X
authors.initials: S
authors.lastname: Trowitzsch
authors.affiliation: Laboratory of Structural Biochemistry, Freie Universität Berlin, Berlin, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Wahl
authors.affiliation: Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.affiliation: Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.affiliation: 1] Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany. [3] Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center, Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zweckstetter
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000648:ultrastructure*; D009690:Nucleic Acid Conformation; D012322:RNA Precursors / Q000235:genetics*; D012326:RNA Splicing; D012331:RNA, Fungal / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000648:ultrastructure; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics / Q000648:ultrastructure*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000648:ultrastructure*; D017381:Spliceosomes / Q000235:genetics
chemical_list: C000595434:BUD13 homolog protein, human; C534389:Bud13 protein, S cerevisiae; D002352:Carrier Proteins; C425663:IST3 protein, S cerevisiae; C534390:Pml1 protein, S cerevisiae; D012322:RNA Precursors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins