A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast
FUS is a nucleic acid binding protein that, when mutated, cause a subset of familial amyotrophic lateral sclerosis (ALS). Expression of FUS in yeast recapitulates several pathological features of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, formation of cytopl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Oxford University Press
2020-06-01
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| Series: | G3: Genes, Genomes, Genetics |
| Subjects: | |
| Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.120.401164 |
| _version_ | 1818884009932881920 |
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| author | Elliott Hayden Shuzhen Chen Abagail Chumley Chenyi Xia Quan Zhong Shulin Ju |
| author_facet | Elliott Hayden Shuzhen Chen Abagail Chumley Chenyi Xia Quan Zhong Shulin Ju |
| author_sort | Elliott Hayden |
| collection | DOAJ |
| description | FUS is a nucleic acid binding protein that, when mutated, cause a subset of familial amyotrophic lateral sclerosis (ALS). Expression of FUS in yeast recapitulates several pathological features of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, formation of cytoplasmic inclusions, and cytotoxicity. Genetic screens using the yeast model of FUS have identified yeast genes and their corresponding human homologs suppressing FUS induced toxicity in yeast, neurons and animal models. To expand the search for human suppressor genes of FUS induced toxicity, we carried out a genome-scale genetic screen using a newly constructed library containing 13570 human genes cloned in an inducible yeast-expression vector. Through multiple rounds of verification, we found 37 human genes that, when overexpressed, suppress FUS induced toxicity in yeast. Human genes with DNA or RNA binding functions are overrepresented among the identified suppressor genes, supporting that perturbations of RNA metabolism is a key underlying mechanism of FUS toxicity. |
| first_indexed | 2024-12-19T15:42:44Z |
| format | Article |
| id | doaj.art-cb9f4e81996a406997ba1f39144ca93a |
| institution | Directory Open Access Journal |
| issn | 2160-1836 |
| language | English |
| last_indexed | 2024-12-19T15:42:44Z |
| publishDate | 2020-06-01 |
| publisher | Oxford University Press |
| record_format | Article |
| series | G3: Genes, Genomes, Genetics |
| spelling | doaj.art-cb9f4e81996a406997ba1f39144ca93a2022-12-21T20:15:26ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362020-06-011061843185210.1534/g3.120.4011645A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in YeastElliott HaydenShuzhen ChenAbagail ChumleyChenyi XiaQuan ZhongShulin JuFUS is a nucleic acid binding protein that, when mutated, cause a subset of familial amyotrophic lateral sclerosis (ALS). Expression of FUS in yeast recapitulates several pathological features of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, formation of cytoplasmic inclusions, and cytotoxicity. Genetic screens using the yeast model of FUS have identified yeast genes and their corresponding human homologs suppressing FUS induced toxicity in yeast, neurons and animal models. To expand the search for human suppressor genes of FUS induced toxicity, we carried out a genome-scale genetic screen using a newly constructed library containing 13570 human genes cloned in an inducible yeast-expression vector. Through multiple rounds of verification, we found 37 human genes that, when overexpressed, suppress FUS induced toxicity in yeast. Human genes with DNA or RNA binding functions are overrepresented among the identified suppressor genes, supporting that perturbations of RNA metabolism is a key underlying mechanism of FUS toxicity.http://g3journal.org/lookup/doi/10.1534/g3.120.401164fusalshuman gene suppressorsyeastgenetic screen |
| spellingShingle | Elliott Hayden Shuzhen Chen Abagail Chumley Chenyi Xia Quan Zhong Shulin Ju A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast G3: Genes, Genomes, Genetics fus als human gene suppressors yeast genetic screen |
| title | A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast |
| title_full | A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast |
| title_fullStr | A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast |
| title_full_unstemmed | A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast |
| title_short | A Genetic Screen for Human Genes Suppressing FUS Induced Toxicity in Yeast |
| title_sort | genetic screen for human genes suppressing fus induced toxicity in yeast |
| topic | fus als human gene suppressors yeast genetic screen |
| url | http://g3journal.org/lookup/doi/10.1534/g3.120.401164 |
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