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dc.contributor.authorGuisbert, Karen S.Kim
dc.contributor.authorGuisbert, Eric
dc.date.accessioned2017-10-12T16:30:44Z
dc.date.available2017-10-12T16:30:44Z
dc.date.issued2017-04-26
dc.identifier.citationGuisbert, K.S.K., Guisbert, E. SF3B1 is a stress-sensitive splicing factor that regulates both HSF1 concentration and activity (2017) PLoS ONE, 12 (4), art. no. e0176382, . Cited 1 time.en_US
dc.identifier.otherhttp://hdl.handle.net/11141/2110 had been assigned to a duplicate entry for this item in this repository. It has been withdrawn.
dc.identifier.urihttp://hdl.handle.net/11141/1875
dc.descriptionDNA binding proteine, poxideheat shock transcription factor, macrolide, messenger RNA, phosphoprotein, pladienolide B, RNA splicing factor, SF3B1 protein, human, small interfering RNA, transcription factoren_US
dc.description.abstractThe heat shock response (HSR) is a well-conserved, cytoprotective stress response that activates the HSF1 transcription factor. During severe stress, cells inhibit mRNA splicing which also serves a cytoprotective function via inhibition of gene expression. Despite their functional interconnectedness, there have not been any previous reports of crosstalk between these two pathways. In a genetic screen, we identified SF3B1, a core component of the U2 snRNP subunit of the spliceosome, as a regulator of the heat shock response in Caenorhabditis elegans. Here, we show that this regulatory connection is conserved in cultured human cells and that there are at least two distinct pathways by which SF3B1 can regulate the HSR. First, inhibition of SF3B1 with moderate levels of Pladienolide B, a previously established small molecule inhibitor of SF3B1, affects the transcriptional activation of HSF1, the transcription factor that mediates the HSR. However, both higher levels of Pladienolide B and SF3B1 siRNA knockdown also change the concentration of HSF1, a form of HSR regulation that has not been previously documented during normal physiology but is observed in some forms of cancer. Intriguingly, mutations in SF3B1 have also been associated with several distinct types of cancer. Finally, we show that regulation of alternative splicing by SF3B1 is sensitive to temperature, providing a new mechanism by which temperature stress can remodel the transcriptome. © 2017 Kim Guisbert, Guisbert. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.description.sponsorshipPublication of this article was funded in part by the Open Access Subvention Fund and the Florida Tech Libraries.
dc.language.isoen_USen_US
dc.rights© 2017 the Authors. Licensed under Creative Commons Attribution Licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleSF3B1 is a stress-sensitive splicing factor that regulates both HSF1 concentration and activityen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pone.0176382


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© 2017 the Authors.  Licensed under Creative Commons Attribution License
Except where otherwise noted, this item's license is described as © 2017 the Authors. Licensed under Creative Commons Attribution License