Composition-based prediction and rational manipulation of prion-like domain recruitment to stress granules

Proceedings of the National Academy of Sciences of the United States of America
Amy E BoncellaEric D Ross

Abstract

Mutations in a number of stress granule-associated proteins have been linked to various neurodegenerative diseases. Several of these mutations are found in aggregation-prone prion-like domains (PrLDs) within these proteins. In this work, we examine the sequence features governing PrLD localization to stress granules upon stress. We demonstrate that many yeast PrLDs are sufficient for stress-induced assembly into microscopically visible foci that colocalize with stress granule markers. Additionally, compositional biases exist among PrLDs that assemble upon stress, and these biases are consistent across different stressors. Using these biases, we have developed a composition-based prediction method that accurately predicts PrLD assembly into foci upon heat shock. We show that compositional changes alter PrLD assembly behavior in a predictable manner, while scrambling primary sequence has little effect on PrLD assembly and recruitment to stress granules. Furthermore, we were able to design synthetic PrLDs that were efficiently recruited to stress granules, and found that aromatic amino acids, which have previously been linked to PrLD phase separation, were dispensable for this recruitment. These results highlight the flexible sequ...Continue Reading

References

Jul 30, 2004·Molecular and Cellular Biology·Eric D RossReed B Wickner
Sep 17, 2004·Molecular Biology of the Cell·Natalie GilksPaul Anderson
Aug 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Eric D RossReed B Wickner
Oct 6, 2006·Bioinformatics·Oxana V GalzitskayaMichail Yu Lobanov
Nov 5, 2008·The Journal of Cell Biology·J Ross BuchanRoy Parker
Nov 4, 2009·Molecular and Cellular Biology·James A ToombsEric D Ross
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lukasz GoldschmidtDavid Eisenberg
Aug 21, 2013·Cell·Mani RamaswamiRoy Parker
Sep 14, 2013·Trends in Biochemical Sciences·Nancy KedershaPaul Anderson
Jan 7, 2014·Cellular and Molecular Life Sciences : CMLS·Sean M Cascarina, Eric D Ross
Mar 4, 2014·PloS One·Aaron C Gonzalez NelsonEric D Ross
May 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Shana Elbaum-GarfinkleClifford P Brangwynne
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kacy R PaulEric D Ross
Sep 24, 2015·G3 : Genes - Genomes - Genetics·Gregory A CaryAimée M Dudley
Jun 13, 2016·Trends in Cell Biology·David S W Protter, Roy Parker
Feb 1, 2017·Molecular and Cellular Biology·Kacy R PaulEric D Ross
Apr 11, 2017·PLoS Computational Biology·Fayyaz Ul Amir Afsar MinhasAsa Ben-Hur
Jan 6, 2018·Science·Titus M FranzmannSimon Alberti

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Citations

Jan 31, 2021·International Journal of Molecular Sciences·Anastasia Fomicheva, Eric D Ross
Jan 12, 2021·Trends in Biochemical Sciences·Shon A LevkovichDana Laor Bar-Yosef
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Pureum Jeon, Jin A Lee
May 4, 2021·Journal of Proteome Research·Lucas VuChristine Vande Velde
May 2, 2021·RNA·Leah E Escalante, Audrey P Gasch
Jul 13, 2021·Frontiers in Aging Neuroscience·Mohammad Reza AsadiMaryam Rezazadeh
Sep 8, 2021·Frontiers in Molecular Biosciences·Valentín IglesiasSalvador Ventura

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Methods Mentioned

BETA
Fluorescence microscopy

Software Mentioned

IUPred
Scipy
PAPA
FoldUnfold
Excel
Python
Seaborn
Matplotlib
PLAAC
house

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