The RNA-Binding Protein Rasputin/G3BP Enhances the Stability and Translation of Its Target mRNAs
John D. Laver,
Jimmy Ly,
Allison K. Winn,
Angelo Karaiskakis,
Sichun Lin,
Kun Nie,
Giulia Benic,
Nima Jaberi-Lashkari,
Wen Xi Cao,
Alireza Khademi,
J. Timothy Westwood,
Sachdev S. Sidhu,
Quaid Morris,
Stephane Angers,
Craig A. Smibert,
Howard D. Lipshitz
Affiliations
John D. Laver
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Jimmy Ly
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Allison K. Winn
Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Angelo Karaiskakis
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Sichun Lin
Department of Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, ON M5S 3M2, Canada
Kun Nie
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Giulia Benic
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Nima Jaberi-Lashkari
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Wen Xi Cao
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
Alireza Khademi
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada
J. Timothy Westwood
Department of Biology, University of Toronto, 3359 Mississauga, Mississauga, ON L5L 1C6, Canada
Sachdev S. Sidhu
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada
Quaid Morris
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada; Vector Institute, 661 University Ave, Toronto, Ontario, Canada, M160 College Street, Toronto, ON M5G 1M1, Canada
Stephane Angers
Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Department of Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, ON M5S 3M2, Canada
Craig A. Smibert
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Department of Biochemistry, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Corresponding author
Howard D. Lipshitz
Department of Molecular Genetics, University of Toronto, 661 University Avenue, Toronto, ON M5G 1M1, Canada; Corresponding author
Summary: G3BP RNA-binding proteins are important components of stress granules (SGs). Here, we analyze the role of the Drosophila G3BP Rasputin (RIN) in unstressed cells, where RIN is not SG associated. Immunoprecipitation followed by microarray analysis identifies over 550 mRNAs that copurify with RIN. The mRNAs found in SGs are long and translationally silent. In contrast, we find that RIN-bound mRNAs, which encode core components of the transcription, splicing, and translation machinery, are short, stable, and highly translated. We show that RIN is associated with polysomes and provide evidence for a direct role for RIN and its human homologs in stabilizing and upregulating the translation of their target mRNAs. We propose that when cells are stressed, the resulting incorporation of RIN/G3BPs into SGs sequesters them away from their short target mRNAs. This would downregulate the expression of these transcripts, even though they are not incorporated into stress granules. : Laver et al. show that in early embryos, Rasputin, the Drosophila G3BP ortholog, binds short mRNAs and is associated with polysomes. They provide evidence for a direct role for Rasputin and its human homologs in stabilizing and upregulating the translation of their target mRNAs. Keywords: RNA-binding protein, post-transcriptional regulation, mRNA translation, mRNA stability, stress granule, Drosophila, embryo, G3BP, Rasputin
