The RNA-Binding Protein Scp160p Facilitates Aggregation of Many Endogenous Q/N-Rich Proteins
Matthew H.K. Cheng,
Patrick C. Hoffmann,
Mirita Franz-Wachtel,
Carola Sparn,
Charlotte Seng,
Boris Maček,
Ralf-Peter Jansen
Affiliations
Matthew H.K. Cheng
International Max Planck Research School “From Molecules to Organisms,” Spemannstraße 35, 72076 Tübingen, Germany; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler Straße 4, 72076 Tübingen, Germany
Patrick C. Hoffmann
Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler Straße 4, 72076 Tübingen, Germany; MRC Laboratory of Molecular Biology, Francis Crick Avenue, CB2 0QH Cambridge, UK
Mirita Franz-Wachtel
Proteome Center Tübingen, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Carola Sparn
Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler Straße 4, 72076 Tübingen, Germany; DKFZ, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Charlotte Seng
Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler Straße 4, 72076 Tübingen, Germany
Boris Maček
International Max Planck Research School “From Molecules to Organisms,” Spemannstraße 35, 72076 Tübingen, Germany; Proteome Center Tübingen, University of Tübingen, Auf der Morgenstelle 15, 72076 Tübingen, Germany
Ralf-Peter Jansen
International Max Planck Research School “From Molecules to Organisms,” Spemannstraße 35, 72076 Tübingen, Germany; Interfaculty Institute of Biochemistry, University of Tübingen, Hoppe-Seyler Straße 4, 72076 Tübingen, Germany; Corresponding author
Summary: The RNA-binding protein Scp160p is the yeast homolog of the conserved vigilin protein family. These proteins influence a variety of nuclear and cytoplasmic functions. One of Scp160p’s reported roles is to increase translation elongation efficiency in a manner related to codon usage. Thus, it can affect translation speed and co-translational folding of nascent peptides. We used polyglutamine (polyQ) reporters to assess Scp160p’s effect on protein synthesis and observed that, in the absence of Scp160p, aggregation of polyQ is reduced and toxicity is abolished. We additionally took a proteomic approach and analyzed the impact of Scp160p on the aggregation of endogenous proteins under normal growth conditions. In the absence of Scp160p, aggregation of many Q/N-rich proteins was reduced. Because aggregation mediated by these regions can be important for the proteins’ functions, Scp160p may affect many processes via aggregation of Q/N-rich proteins. : Glutamine and asparagine (Q/N)-mediated protein aggregation can lead to neurodegenerative diseases but is also functionally important. Cheng et al. report a method to assess aggregation of proteins at the proteomic level and observe reduced aggregation of many endogenous Q/N-rich proteins in the absence of the yeast vigilin protein. Keywords: vigilin, polyglutamine, protein aggregation, codon usage, low complexity regions, SCP160
