An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs.
Spliceosomal small nuclear ribonucleoproteins (snRNPs) are essential components of the nuclear pre-mRNA processing machinery. A hallmark of these particles is a ring-shaped core domain generated by the binding of Sm proteins onto snRNA. PRMT5 and SMN complexes mediate the formation of the core domain in vivo. Here, we have elucidated the mechanism of this reaction by both biochemical and structural studies. We show that pICln, a component of the PRMT5 complex, induces the formation of an otherwise unstable higher-order Sm protein unit. In this state, the Sm proteins are kinetically trapped, preventing their association with snRNA. The SMN complex subsequently binds to these Sm protein units, dissociates pICln, and catalyzes ring closure on snRNA. Our data identify pICln as an assembly chaperone and the SMN complex as a catalyst of spliceosomal snRNP formation. The mode of action of this combined chaperone/catalyst system is reminiscent of the mechanism employed by DNA clamp loaders.
Chari
Ashwin
A
Department of Biochemistry, Biocenter, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
Golas
Monika M
MM
Klingenhäger
Michael
M
Neuenkirchen
Nils
N
Sander
Bjoern
B
Englbrecht
Clemens
C
Sickmann
Albert
A
Stark
Holger
H
Fischer
Utz
U
D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry / Q000378:metabolism*; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism
C108381:GEMIN2 protein, human; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D017411:Ribonucleoproteins, Small Nuclear; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D012313:RNA; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases