Nucleoporins shape germ granule architecture and balance small RNA silencing pathways
Abstract Animals use small RNA pathways, such as PIWI-interacting RNA (piRNA) and small interfering RNA (siRNA), to silence harmful genetic elements. In Caenorhabditis elegans, piRNA pathway components are organized into sub-compartments within germ granules near nuclear pore complexes, but the basi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59526-3 |
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| author | Kun Shi Ying Zhang Zhenzhen Du Symonne C. Liu Ivan Leon Xinyu Fan Heng-Chi Lee Donglei Zhang |
| author_facet | Kun Shi Ying Zhang Zhenzhen Du Symonne C. Liu Ivan Leon Xinyu Fan Heng-Chi Lee Donglei Zhang |
| author_sort | Kun Shi |
| collection | DOAJ |
| description | Abstract Animals use small RNA pathways, such as PIWI-interacting RNA (piRNA) and small interfering RNA (siRNA), to silence harmful genetic elements. In Caenorhabditis elegans, piRNA pathway components are organized into sub-compartments within germ granules near nuclear pore complexes, but the basis and function of this association have remained unclear. Here, our data suggest that germ granule formation and nuclear pore clustering are interdependent processes. We identify the conserved nucleoporins NPP-14/NUP214 and NPP-24/NUP88, along with the germ granule protein EPS-1, as key factors anchoring germ granules to nuclear pores. Loss of these factors leads to disorganized, fused granules and enhanced piRNA silencing. Artificial tethering of granule sub-compartments mimics this effect. However, this increase in piRNA silencing comes at the expense of RNA interference efficiency and heritability. Our findings reveal the molecular factors mediating germ granule–nuclear pore interaction and highlight how spatial organization of RNA silencing machinery fine-tunes gene regulation. |
| format | Article |
| id | doaj-art-077b7434d996469d9981d34697d7e3ff |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-077b7434d996469d9981d34697d7e3ff2025-08-20T03:53:22ZengNature PortfolioNature Communications2041-17232025-05-0116111810.1038/s41467-025-59526-3Nucleoporins shape germ granule architecture and balance small RNA silencing pathwaysKun Shi0Ying Zhang1Zhenzhen Du2Symonne C. Liu3Ivan Leon4Xinyu Fan5Heng-Chi Lee6Donglei Zhang7Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Molecular Genetics and Cell Biology, University of ChicagoDepartment of Molecular Genetics and Cell Biology, University of ChicagoDepartment of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Molecular Genetics and Cell Biology, University of ChicagoDepartment of Molecular Genetics and Cell Biology, University of ChicagoAbstract Animals use small RNA pathways, such as PIWI-interacting RNA (piRNA) and small interfering RNA (siRNA), to silence harmful genetic elements. In Caenorhabditis elegans, piRNA pathway components are organized into sub-compartments within germ granules near nuclear pore complexes, but the basis and function of this association have remained unclear. Here, our data suggest that germ granule formation and nuclear pore clustering are interdependent processes. We identify the conserved nucleoporins NPP-14/NUP214 and NPP-24/NUP88, along with the germ granule protein EPS-1, as key factors anchoring germ granules to nuclear pores. Loss of these factors leads to disorganized, fused granules and enhanced piRNA silencing. Artificial tethering of granule sub-compartments mimics this effect. However, this increase in piRNA silencing comes at the expense of RNA interference efficiency and heritability. Our findings reveal the molecular factors mediating germ granule–nuclear pore interaction and highlight how spatial organization of RNA silencing machinery fine-tunes gene regulation.https://doi.org/10.1038/s41467-025-59526-3 |
| spellingShingle | Kun Shi Ying Zhang Zhenzhen Du Symonne C. Liu Ivan Leon Xinyu Fan Heng-Chi Lee Donglei Zhang Nucleoporins shape germ granule architecture and balance small RNA silencing pathways Nature Communications |
| title | Nucleoporins shape germ granule architecture and balance small RNA silencing pathways |
| title_full | Nucleoporins shape germ granule architecture and balance small RNA silencing pathways |
| title_fullStr | Nucleoporins shape germ granule architecture and balance small RNA silencing pathways |
| title_full_unstemmed | Nucleoporins shape germ granule architecture and balance small RNA silencing pathways |
| title_short | Nucleoporins shape germ granule architecture and balance small RNA silencing pathways |
| title_sort | nucleoporins shape germ granule architecture and balance small rna silencing pathways |
| url | https://doi.org/10.1038/s41467-025-59526-3 |
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