The RNA-binding protein, Rasputin/G3BP, enhances the stability and translation of its target mRNAs

Laver, J. D.; Ly, J.; Winn, A. K.; Karaiskakis, A.; Lin, S.; Nie, K.; Benic, G.; Jaberi-Lashkari, N.; Cao, W. X.; Khademi, A.; Westwood, J. T.; Sidhu, S. S.; Morris, Q.; Angers, S.; Smibert, C. A.; Lipshitz, H. D.

doi:10.1101/2020.01.21.913079

bioRxiv · 10.1101/2020.01.21.913079

The RNA-binding protein, Rasputin/G3BP, enhances the stability and translation of its target mRNAs

Laver, J. D.·Ly, J.·Winn, A. K.·Karaiskakis, A.·Lin, S.·Nie, K.·Benic, G.·Jaberi-Lashkari, N.·Cao, W. X.·Khademi, A.·Westwood, J. T.·Sidhu, S. S.·Morris, Q.·Angers, S.·Smibert, C. A.·Lipshitz, H. D.

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Abstract

G3BP RNA-binding proteins are important components of stress granules (SGs). Here we analyze the role of Drosophila G3BP, Rasputin (RIN), in unstressed cells, where RIN is not SG associated. Immunoprecipitation followed by microarray analysis identified 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.

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Laver, J. D., Ly, J., Winn, A. K., Karaiskakis, A., Lin, S., Nie, K., Benic, G., Jaberi-Lashkari, N., Cao, W. X., Khademi, A., Westwood, J. T., Sidhu, S. S., Morris, Q., Angers, S., Smibert, C. A., Lipshitz, H. D.. 2020-01-21. The RNA-binding protein, Rasputin/G3BP, enhances the stability and translation of its target mRNAs. https://doi.org/10.1101/2020.01.21.913079

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