title: The Ribosome Cooperates with the Assembly Chaperone pICln to Initiate Formation of snRNPs.
abstract: The formation of macromolecular complexes within the crowded environment of cells often requires aid from assembly chaperones. PRMT5 and SMN complexes mediate this task for the assembly of the common core of pre-mRNA processing small nuclear ribonucleoprotein particles (snRNPs). Core formation is initiated by the PRMT5-complex subunit pICln, which pre-arranges the core proteins into spatial positions occupied in the assembled snRNP. The SMN complex then accepts these pICln-bound proteins and unites them with small nuclear RNA (snRNA). Here, we have analyzed how newly synthesized snRNP proteins are channeled into the assembly pathway to evade mis-assembly. We show that they initially remain bound to the ribosome near the polypeptide exit tunnel and dissociate upon association with pICln. Coincident with its release activity, pICln ensures the formation of cognate heterooligomers and their chaperoned guidance into the assembly pathway. Our study identifies the ribosomal quality control hub as a site where chaperone-mediated assembly of macromolecular complexes can be initiated.
authors.affiliation: Department of Biochemistry, University of Wuerzburg, 97074 Wuerzburg, Germany; Department for Structural Dynamics, Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
authors.forename: Elham
authors.initials: E
authors.lastname: Paknia
authors.affiliation: Department for Structural Dynamics, Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany. Electronic address: ashwin.chari@mpibpc.mpg.de.
authors.forename: Ashwin
authors.initials: A
authors.lastname: Chari
authors.affiliation: Department for Structural Dynamics, Max-Planck-Institute for Biophysical Chemistry, 37077 Goettingen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Department of Biochemistry, University of Wuerzburg, 97074 Wuerzburg, Germany; Department of Radiation Medicine and Applied Sciences, University of California at San Diego, San Diego, CA 92037, USA. Electronic address: utz.fischer@biozentrum.uni-wuerzburg.de.
authors.forename: Utz
authors.initials: U
authors.lastname: Fischer
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000096:biosynthesis*; D012270:Ribosomes / Q000378:metabolism*
chemical_list: C410035:CLNS1A protein, human; D007473:Ion Channels; D046911:Macromolecular Substances; D017411:Ribonucleoproteins, Small Nuclear
keywords: assembly chaperone; pICln; ribosome; snRNPs