Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans
The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may se...
| Main Authors: | , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2017
|
| Online Access: | http://hdl.handle.net/1721.1/107842 https://orcid.org/0000-0002-8840-3802 https://orcid.org/0000-0001-8281-6916 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4109-5152 |
| _version_ | 1826196530466390016 |
|---|---|
| author | Cattie, Douglas John Richardson, Claire Elissa Reddy, Kirthi C. Ness-Cohn, Elan M. Droste, Rita Thompson, Mary Katherine Gilbert, Wendy Kim, Dennis H. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Cattie, Douglas John Richardson, Claire Elissa Reddy, Kirthi C. Ness-Cohn, Elan M. Droste, Rita Thompson, Mary Katherine Gilbert, Wendy Kim, Dennis H. |
| author_sort | Cattie, Douglas John |
| collection | MIT |
| description | The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously described mutations in genes encoding translation initiation components that confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or eif-3.L are viable, and mutants show normal rates of growth and development, and have wild-type levels of bulk protein synthesis. Lifespan extension resulting from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead family transcription factor DAF-16. Mutations in eif-3.K or eif-3.L also confer enhanced resistance to ER stress, independent of IRE-1-XBP-1, ATF-6, and PEK-1, and independent of DAF-16. Our data suggest a pivotal functional role for conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of cellular and organismal responses to ER stress and aging |
| first_indexed | 2024-09-23T10:28:48Z |
| format | Article |
| id | mit-1721.1/107842 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:28:48Z |
| publishDate | 2017 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1078422022-09-27T09:44:47Z Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans Cattie, Douglas John Richardson, Claire Elissa Reddy, Kirthi C. Ness-Cohn, Elan M. Droste, Rita Thompson, Mary Katherine Gilbert, Wendy Kim, Dennis H. Massachusetts Institute of Technology. Department of Biology Cattie, Douglas John Richardson, Claire Elissa Reddy, Kirthi C. Ness-Cohn, Elan M. Droste, Rita Thompson, Mary Katherine Gilbert, Wendy Kim, Dennis H. The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously described mutations in genes encoding translation initiation components that confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or eif-3.L are viable, and mutants show normal rates of growth and development, and have wild-type levels of bulk protein synthesis. Lifespan extension resulting from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead family transcription factor DAF-16. Mutations in eif-3.K or eif-3.L also confer enhanced resistance to ER stress, independent of IRE-1-XBP-1, ATF-6, and PEK-1, and independent of DAF-16. Our data suggest a pivotal functional role for conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of cellular and organismal responses to ER stress and aging National Institutes of Health (U.S.) (Grant R01-GM084477) National Institutes of Health (U.S.) (Pre-Doctoral Training Grant T32GM007287) 2017-04-05T14:17:29Z 2017-04-05T14:17:29Z 2016-09 2016-03 Article http://purl.org/eprint/type/JournalArticle 1553-7404 http://hdl.handle.net/1721.1/107842 Cattie, Douglas J. et al. “Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis Elegans.” Ed. Gregory P. Copenhaver. PLOS Genetics 12.9 (2016): e1006326. https://orcid.org/0000-0002-8840-3802 https://orcid.org/0000-0001-8281-6916 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4109-5152 en_US http://dx.doi.org/10.1371/journal.pgen.1006326 PLOS Genetics Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLoS |
| spellingShingle | Cattie, Douglas John Richardson, Claire Elissa Reddy, Kirthi C. Ness-Cohn, Elan M. Droste, Rita Thompson, Mary Katherine Gilbert, Wendy Kim, Dennis H. Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title | Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title_full | Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title_fullStr | Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title_full_unstemmed | Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title_short | Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans |
| title_sort | mutations in nonessential eif3k and eif3l genes confer lifespan extension and enhanced resistance to er stress in caenorhabditis elegans |
| url | http://hdl.handle.net/1721.1/107842 https://orcid.org/0000-0002-8840-3802 https://orcid.org/0000-0001-8281-6916 https://orcid.org/0000-0003-2807-9657 https://orcid.org/0000-0002-4109-5152 |
| work_keys_str_mv | AT cattiedouglasjohn mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT richardsonclaireelissa mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT reddykirthic mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT nesscohnelanm mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT drosterita mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT thompsonmarykatherine mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT gilbertwendy mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans AT kimdennish mutationsinnonessentialeif3kandeif3lgenesconferlifespanextensionandenhancedresistancetoerstressincaenorhabditiselegans |