Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging.
Argonaute (AGO) proteins partner with microRNAs (miRNAs) to target specific genes for post-transcriptional regulation. During larval development in Caenorhabditis elegans, Argonaute-Like Gene 1 (ALG-1) is the primary mediator of the miRNA pathway, while the related ALG-2 protein is largely dispensab...
| Glavni autori: | , , , , , , |
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| Format: | Članak |
| Jezik: | English |
| Izdano: |
Public Library of Science (PLoS)
2018-06-01
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| Serija: | PLoS Genetics |
| Online pristup: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007379&type=printable |
| _version_ | 1826579508494336000 |
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| author | Antti P Aalto Ian A Nicastro James P Broughton Laura B Chipman William P Schreiner Jerry S Chen Amy E Pasquinelli |
| author_facet | Antti P Aalto Ian A Nicastro James P Broughton Laura B Chipman William P Schreiner Jerry S Chen Amy E Pasquinelli |
| author_sort | Antti P Aalto |
| collection | DOAJ |
| description | Argonaute (AGO) proteins partner with microRNAs (miRNAs) to target specific genes for post-transcriptional regulation. During larval development in Caenorhabditis elegans, Argonaute-Like Gene 1 (ALG-1) is the primary mediator of the miRNA pathway, while the related ALG-2 protein is largely dispensable. Here we show that in adult C. elegans these AGOs are differentially expressed and, surprisingly, work in opposition to each other; alg-1 promotes longevity, whereas alg-2 restricts lifespan. Transcriptional profiling of adult animals revealed that distinct miRNAs and largely non-overlapping sets of protein-coding genes are misregulated in alg-1 and alg-2 mutants. Interestingly, many of the differentially expressed genes are downstream targets of the Insulin/ IGF-1 Signaling (IIS) pathway, which controls lifespan by regulating the activity of the DAF-16/ FOXO transcription factor. Consistent with this observation, we show that daf-16 is required for the extended lifespan of alg-2 mutants. Furthermore, the long lifespan of daf-2 insulin receptor mutants, which depends on daf-16, is strongly reduced in animals lacking alg-1 activity. This work establishes an important role for AGO-mediated gene regulation in aging C. elegans and illustrates that the activity of homologous genes can switch from complementary to antagonistic, depending on the life stage. |
| first_indexed | 2024-12-19T06:45:35Z |
| format | Article |
| id | doaj.art-ad23563c739c482fa2fcb1cd2fc9bc5c |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2025-03-14T14:19:24Z |
| publishDate | 2018-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-ad23563c739c482fa2fcb1cd2fc9bc5c2025-02-27T05:32:20ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-06-01146e100737910.1371/journal.pgen.1007379Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging.Antti P AaltoIan A NicastroJames P BroughtonLaura B ChipmanWilliam P SchreinerJerry S ChenAmy E PasquinelliArgonaute (AGO) proteins partner with microRNAs (miRNAs) to target specific genes for post-transcriptional regulation. During larval development in Caenorhabditis elegans, Argonaute-Like Gene 1 (ALG-1) is the primary mediator of the miRNA pathway, while the related ALG-2 protein is largely dispensable. Here we show that in adult C. elegans these AGOs are differentially expressed and, surprisingly, work in opposition to each other; alg-1 promotes longevity, whereas alg-2 restricts lifespan. Transcriptional profiling of adult animals revealed that distinct miRNAs and largely non-overlapping sets of protein-coding genes are misregulated in alg-1 and alg-2 mutants. Interestingly, many of the differentially expressed genes are downstream targets of the Insulin/ IGF-1 Signaling (IIS) pathway, which controls lifespan by regulating the activity of the DAF-16/ FOXO transcription factor. Consistent with this observation, we show that daf-16 is required for the extended lifespan of alg-2 mutants. Furthermore, the long lifespan of daf-2 insulin receptor mutants, which depends on daf-16, is strongly reduced in animals lacking alg-1 activity. This work establishes an important role for AGO-mediated gene regulation in aging C. elegans and illustrates that the activity of homologous genes can switch from complementary to antagonistic, depending on the life stage.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007379&type=printable |
| spellingShingle | Antti P Aalto Ian A Nicastro James P Broughton Laura B Chipman William P Schreiner Jerry S Chen Amy E Pasquinelli Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. PLoS Genetics |
| title | Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. |
| title_full | Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. |
| title_fullStr | Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. |
| title_full_unstemmed | Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. |
| title_short | Opposing roles of microRNA Argonautes during Caenorhabditis elegans aging. |
| title_sort | opposing roles of microrna argonautes during caenorhabditis elegans aging |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007379&type=printable |
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