Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition
Summary: The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a role promoting the evolution of new heritable traits. To better understand how Hsp90 can affect mRNA translation, we screen more than 1,600 factors involved in mRNA regulation for physical interact...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720309864 |
| _version_ | 1818269303965745152 |
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| author | Peter Tsvetkov Timothy J. Eisen Sven U. Heinrich Zarina Brune Erinc Hallacli Greg A. Newby Can Kayatekin David Pincus Susan Lindquist |
| author_facet | Peter Tsvetkov Timothy J. Eisen Sven U. Heinrich Zarina Brune Erinc Hallacli Greg A. Newby Can Kayatekin David Pincus Susan Lindquist |
| author_sort | Peter Tsvetkov |
| collection | DOAJ |
| description | Summary: The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a role promoting the evolution of new heritable traits. To better understand how Hsp90 can affect mRNA translation, we screen more than 1,600 factors involved in mRNA regulation for physical interactions with Hsp90 in human cells. The mRNA binding protein CPEB2 strongly binds Hsp90 via its prion domain. In a yeast model, transient inhibition of Hsp90 results in persistent activation of a CPEB translation reporter even in the absence of exogenous CPEB that persists for 30 generations after the inhibitor is removed. Ribosomal profiling reveals that some endogenous yeast mRNAs, including HAC1, show a persistent change in translation efficiency following transient Hsp90 inhibition. Thus, transient loss of Hsp90 function can promote a nongenetic inheritance of a translational state affecting specific mRNAs, introducing a mechanism by which Hsp90 can promote phenotypic variation. |
| first_indexed | 2024-12-12T20:52:15Z |
| format | Article |
| id | doaj.art-7ac8c65540344e49a4c7c6c9a8211d69 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T20:52:15Z |
| publishDate | 2020-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7ac8c65540344e49a4c7c6c9a8211d692022-12-22T00:12:23ZengElsevierCell Reports2211-12472020-08-01326108001Persistent Activation of mRNA Translation by Transient Hsp90 InhibitionPeter Tsvetkov0Timothy J. Eisen1Sven U. Heinrich2Zarina Brune3Erinc Hallacli4Greg A. Newby5Can Kayatekin6David Pincus7Susan Lindquist8Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Corresponding authorWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USASummary: The heat shock protein 90 (Hsp90) chaperone functions as a protein-folding buffer and plays a role promoting the evolution of new heritable traits. To better understand how Hsp90 can affect mRNA translation, we screen more than 1,600 factors involved in mRNA regulation for physical interactions with Hsp90 in human cells. The mRNA binding protein CPEB2 strongly binds Hsp90 via its prion domain. In a yeast model, transient inhibition of Hsp90 results in persistent activation of a CPEB translation reporter even in the absence of exogenous CPEB that persists for 30 generations after the inhibitor is removed. Ribosomal profiling reveals that some endogenous yeast mRNAs, including HAC1, show a persistent change in translation efficiency following transient Hsp90 inhibition. Thus, transient loss of Hsp90 function can promote a nongenetic inheritance of a translational state affecting specific mRNAs, introducing a mechanism by which Hsp90 can promote phenotypic variation.http://www.sciencedirect.com/science/article/pii/S2211124720309864prionsepigentic regualtioncellular memorymRNA translationHsp90yeast |
| spellingShingle | Peter Tsvetkov Timothy J. Eisen Sven U. Heinrich Zarina Brune Erinc Hallacli Greg A. Newby Can Kayatekin David Pincus Susan Lindquist Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition Cell Reports prions epigentic regualtion cellular memory mRNA translation Hsp90 yeast |
| title | Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition |
| title_full | Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition |
| title_fullStr | Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition |
| title_full_unstemmed | Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition |
| title_short | Persistent Activation of mRNA Translation by Transient Hsp90 Inhibition |
| title_sort | persistent activation of mrna translation by transient hsp90 inhibition |
| topic | prions epigentic regualtion cellular memory mRNA translation Hsp90 yeast |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720309864 |
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