The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing
Summary: Argonaute/small RNA pathways and heterochromatin work together to propagate transgenerational gene silencing, but the mechanisms behind their interaction are not well understood. Here, we show that induction of heterochromatin silencing in C. elegans by RNAi or by artificially tethering pat...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004199 |
| _version_ | 1797842455010213888 |
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| author | Yue-He Ding Humberto J. Ochoa Takao Ishidate Masaki Shirayama Craig C. Mello |
| author_facet | Yue-He Ding Humberto J. Ochoa Takao Ishidate Masaki Shirayama Craig C. Mello |
| author_sort | Yue-He Ding |
| collection | DOAJ |
| description | Summary: Argonaute/small RNA pathways and heterochromatin work together to propagate transgenerational gene silencing, but the mechanisms behind their interaction are not well understood. Here, we show that induction of heterochromatin silencing in C. elegans by RNAi or by artificially tethering pathway components to target RNA causes co-localization of target alleles in pachytene nuclei. Tethering the nuclear Argonaute WAGO-9/HRDE-1 induces heterochromatin formation and independently induces small RNA amplification. Consistent with this finding, HRDE-1, while predominantly nuclear, also localizes to peri-nuclear nuage domains, where amplification is thought to occur. Tethering a heterochromatin-silencing factor, NRDE-2, induces heterochromatin formation, which subsequently causes de novo synthesis of HRDE-1 guide RNAs. HRDE-1 then acts to further amplify small RNAs that load on downstream Argonautes. These findings suggest that HRDE-1 plays a dual role, acting upstream to initiate heterochromatin silencing and downstream to stimulate a new cycle of small RNA amplification, thus establishing a self-enforcing mechanism that propagates gene silencing to future generations. |
| first_indexed | 2024-04-09T16:48:10Z |
| format | Article |
| id | doaj.art-9736d36d55134e42911df4acf028d412 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T16:48:10Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9736d36d55134e42911df4acf028d4122023-04-22T06:20:51ZengElsevierCell Reports2211-12472023-05-01425112408The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencingYue-He Ding0Humberto J. Ochoa1Takao Ishidate2Masaki Shirayama3Craig C. Mello4RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USARNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USARNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USARNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USARNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA; Corresponding authorSummary: Argonaute/small RNA pathways and heterochromatin work together to propagate transgenerational gene silencing, but the mechanisms behind their interaction are not well understood. Here, we show that induction of heterochromatin silencing in C. elegans by RNAi or by artificially tethering pathway components to target RNA causes co-localization of target alleles in pachytene nuclei. Tethering the nuclear Argonaute WAGO-9/HRDE-1 induces heterochromatin formation and independently induces small RNA amplification. Consistent with this finding, HRDE-1, while predominantly nuclear, also localizes to peri-nuclear nuage domains, where amplification is thought to occur. Tethering a heterochromatin-silencing factor, NRDE-2, induces heterochromatin formation, which subsequently causes de novo synthesis of HRDE-1 guide RNAs. HRDE-1 then acts to further amplify small RNAs that load on downstream Argonautes. These findings suggest that HRDE-1 plays a dual role, acting upstream to initiate heterochromatin silencing and downstream to stimulate a new cycle of small RNA amplification, thus establishing a self-enforcing mechanism that propagates gene silencing to future generations.http://www.sciencedirect.com/science/article/pii/S2211124723004199CP: Molecular biology |
| spellingShingle | Yue-He Ding Humberto J. Ochoa Takao Ishidate Masaki Shirayama Craig C. Mello The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing Cell Reports CP: Molecular biology |
| title | The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing |
| title_full | The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing |
| title_fullStr | The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing |
| title_full_unstemmed | The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing |
| title_short | The nuclear Argonaute HRDE-1 directs target gene re-localization and shuttles to nuage to promote small RNA-mediated inherited silencing |
| title_sort | nuclear argonaute hrde 1 directs target gene re localization and shuttles to nuage to promote small rna mediated inherited silencing |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723004199 |
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