A higher order PUF complex is central to regulation of C. elegans germline stem cells
Abstract PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex t...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55526-x |
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| author | Chen Qiu Sarah L. Crittenden Brian H. Carrick Lucas B. Dillard Stephany J. Costa Dos Santos Venkata P. Dandey Robert C. Dutcher Elizabeth G. Viverette Robert N. Wine Jennifer Woodworth Zachary T. Campbell Marvin Wickens Mario J. Borgnia Judith Kimble Traci M. Tanaka Hall |
| author_facet | Chen Qiu Sarah L. Crittenden Brian H. Carrick Lucas B. Dillard Stephany J. Costa Dos Santos Venkata P. Dandey Robert C. Dutcher Elizabeth G. Viverette Robert N. Wine Jennifer Woodworth Zachary T. Campbell Marvin Wickens Mario J. Borgnia Judith Kimble Traci M. Tanaka Hall |
| author_sort | Chen Qiu |
| collection | DOAJ |
| description | Abstract PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms. |
| format | Article |
| id | doaj-art-0832099998414d21bf1c8787f164d071 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0832099998414d21bf1c8787f164d0712025-01-05T12:37:47ZengNature PortfolioNature Communications2041-17232025-01-0116111810.1038/s41467-024-55526-xA higher order PUF complex is central to regulation of C. elegans germline stem cellsChen Qiu0Sarah L. Crittenden1Brian H. Carrick2Lucas B. Dillard3Stephany J. Costa Dos Santos4Venkata P. Dandey5Robert C. Dutcher6Elizabeth G. Viverette7Robert N. Wine8Jennifer Woodworth9Zachary T. Campbell10Marvin Wickens11Mario J. Borgnia12Judith Kimble13Traci M. Tanaka Hall14Epigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Biochemistry, University of WisconsinDepartment of Biochemistry, University of WisconsinGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Biochemistry, University of WisconsinGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Biochemistry, University of WisconsinDepartment of Anesthesiology, University of Wisconsin School of Medicine and Public HealthDepartment of Biochemistry, University of WisconsinGenome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthDepartment of Biochemistry, University of WisconsinEpigenetics and RNA Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of HealthAbstract PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF binding elements (FBEs) in its 3′UTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established ‘canonical’ FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discoveries of the LST-1–FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predict an expanded regulatory repertoire of different assemblies of PUF-partner-RNA higher order complexes in nematode GSCs. This also suggests analogous PUF controls may await discovery in other biological contexts and organisms.https://doi.org/10.1038/s41467-024-55526-x |
| spellingShingle | Chen Qiu Sarah L. Crittenden Brian H. Carrick Lucas B. Dillard Stephany J. Costa Dos Santos Venkata P. Dandey Robert C. Dutcher Elizabeth G. Viverette Robert N. Wine Jennifer Woodworth Zachary T. Campbell Marvin Wickens Mario J. Borgnia Judith Kimble Traci M. Tanaka Hall A higher order PUF complex is central to regulation of C. elegans germline stem cells Nature Communications |
| title | A higher order PUF complex is central to regulation of C. elegans germline stem cells |
| title_full | A higher order PUF complex is central to regulation of C. elegans germline stem cells |
| title_fullStr | A higher order PUF complex is central to regulation of C. elegans germline stem cells |
| title_full_unstemmed | A higher order PUF complex is central to regulation of C. elegans germline stem cells |
| title_short | A higher order PUF complex is central to regulation of C. elegans germline stem cells |
| title_sort | higher order puf complex is central to regulation of c elegans germline stem cells |
| url | https://doi.org/10.1038/s41467-024-55526-x |
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