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Caenorhabditis elegans AF4/FMR2 Family Homolog affl-2 Regulates Heat-Shock-Induced Gene Expression

Walton, Sophie J. and Wang, Han and Quintero-Cadena, Porfirio and Bateman, Alex and Sternberg, Paul W. (2020) Caenorhabditis elegans AF4/FMR2 Family Homolog affl-2 Regulates Heat-Shock-Induced Gene Expression. Genetics, 215 (4). pp. 1039-1054. ISSN 0016-6731. https://resolver.caltech.edu/CaltechAUTHORS:20191028-093454817

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Abstract

To mitigate the deleterious effects of temperature increases on cellular organization and proteotoxicity, organisms have developed mechanisms to respond to heat stress. In eukaryotes, HSF1 is the master regulator of the heat shock transcriptional response, but the heat shock response pathway is not yet fully understood. From a forward genetic screen for suppressors of heat-shock-induced gene expression in Caenorhabditis elegans, we found a new allele of hsf-1 that alters its DNA-binding domain, and we found three additional alleles of sup-45, a previously molecularly uncharacterized genetic locus. We identified sup-45 as one of the two hitherto unknown C. elegans orthologs of the human AF4/FMR2 family proteins, which are involved in regulation of transcriptional elongation rate. We thus renamed sup-45 as affl-2 (AF4/FMR2-Like). Through RNA-seq, we demonstrated that affl-2 mutants are deficient in heat-shock-induced transcription. Additionally, affl-2 mutants have herniated intestines, while worms lacking its sole paralog (affl-1) appear wild type. AFFL-2 is a broadly expressed nuclear protein, and nuclear localization of AFFL-2 is necessary for its role in heat shock response. affl-2 and its paralog are not essential for proper HSF-1 expression and localization after heat shock, which suggests that affl-2 may function downstream of, or parallel to, hsf-1. Our characterization of affl-2 provides insights into the regulation of heat-shock-induced gene expression to protect against heat stress.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1534/genetics.120.302923DOIArticle
https://doi.org/10.1101/817833DOIDiscussion Paper
ORCID:
AuthorORCID
Walton, Sophie J.0000-0003-1320-1525
Wang, Han0000-0002-1933-5762
Quintero-Cadena, Porfirio0000-0003-0067-5844
Bateman, Alex0000-0002-6982-4660
Sternberg, Paul W.0000-0002-7699-0173
Alternate Title:Caenorhabditis elegans AF4/FMR2 family homolog affl-2 is required for heat shock induced gene expression
Additional Information:© 2020 by the Genetics Society of America. Manuscript received October 21, 2019; accepted for publication May 27, 2020; published Early Online June 9, 2020. We thank Heenam Park for helping create putative affl-1 null mutants using CRISPR/Cas9, and Jean Badroos, Jasmine S. Revanna, and Minyi Tan for technical assistance. We thank Hillel Schwartz, Jonathan Liu, and members of the Sternberg laboratory for insightful discussions. We thank Sarah MacLean and the Sternberg laboratory members for comments on the manuscript. Some strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the National Institutes of Science (NIH) Office of Research Infrastructure Programs (P40 OD010440). This work was supported by National Institutes of Heath grant (K99GM126137 to H.W., U24HG002223 to P.W.S., and R240D023041). The Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology performed whole genome sequencing and RNA-sequencing. S.J.W. was supported by the Caltech Student Faculty Programs, the family of Laurence J. Stuppy, Samuel N. Vodopia, and Carol J. Hasson.
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
Funders:
Funding AgencyGrant Number
NIHP40 OD010440
NIHK99GM126137
NIHU24HG002223
NIHR240D023041
CaltechUNSPECIFIED
Laurence J. StuppyUNSPECIFIED
Samuel N. VodopiaUNSPECIFIED
Carol J. HassonUNSPECIFIED
Issue or Number:4
Record Number:CaltechAUTHORS:20191028-093454817
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191028-093454817
Official Citation:Caenorhabditis elegans AF4/FMR2 Family Homolog affl-2 Regulates Heat-Shock-Induced Gene Expression. Sophie J. Walton, Han Wang, Porfirio Quintero-Cadena, Alex Bateman and Paul W. Sternberg. GENETICS August 1, 2020 vol. 215 no. 4 1039-1054; https://doi.org/10.1534/genetics.120.302923
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99484
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:28 Oct 2019 16:48
Last Modified:13 Aug 2020 17:55

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