| [PMID]: | 29232700 |
| [Au] Autor: | Shin H; Haupt KA; Kershner AM; Kroll-Conner P; Wickens M; Kimble J |
| [Ad] Endereço: | Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America. |
| [Ti] Título: | SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans. |
| [So] Source: | PLoS Genet;13(12):e1007121, 2017 12. |
| [Is] ISSN: | 1553-7404 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Central questions in regenerative biology include how stem cells are maintained and how they transition from self-renewal to differentiation. Germline stem cells (GSCs) in Caeno-rhabditis elegans provide a tractable in vivo model to address these questions. In this system, Notch signaling and PUF RNA binding proteins, FBF-1 and FBF-2 (collectively FBF), maintain a pool of GSCs in a naïve state. An open question has been how Notch signaling modulates FBF activity to promote stem cell self-renewal. Here we report that two Notch targets, SYGL-1 and LST-1, link niche signaling to FBF. We find that SYGL-1 and LST-1 proteins are cytoplasmic and normally restricted to the GSC pool region. Increasing the distribution of SYGL-1 expands the pool correspondingly, and vast overexpression of either SYGL-1 or LST-1 generates a germline tumor. Thus, SYGL-1 and LST-1 are each sufficient to drive "stemness" and their spatial restriction prevents tumor formation. Importantly, SYGL-1 and LST-1 can only drive tumor formation when FBF is present. Moreover, both proteins interact physically with FBF, and both are required to repress a signature FBF mRNA target. Together, our results support a model in which SYGL-1 and LST-1 form a repressive complex with FBF that is crucial for stem cell maintenance. We further propose that progression from a naïve stem cell state to a state primed for differentiation relies on loss of SYGL-1 and LST-1, which in turn relieves FBF target RNAs from repression. Broadly, our results provide new insights into the link between niche signaling and a downstream RNA regulatory network and how this circuitry governs the balance between self-renewal and differentiation. |
| [Mh] Termos MeSH primário: |
Proteínas de Caenorhabditis elegans/genética
Diferenciação Celular/genética
Autorrenovação Celular/genética
Peptídeo 1 Semelhante ao Glucagon/genética
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| [Mh] Termos MeSH secundário: |
Animais
Caenorhabditis elegans/genética
Caenorhabditis elegans/crescimento & desenvolvimento
Meiose/genética
RNA/genética
RNA Mensageiro/genética
Proteínas de Ligação a RNA/genética
Transdução de Sinais/genética
Células-Tronco/metabolismo
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL |
[Nm] Nome de substância:
| 0 (Caenorhabditis elegans Proteins); 0 (LST-1 protein, C elegans); 0 (RNA, Messenger); 0 (RNA-Binding Proteins); 0 (SYGL-1 protein, C elegans); 63231-63-0 (RNA); 89750-14-1 (Glucagon-Like Peptide 1) |
| [Em] Mês de entrada: | 1801 |
| [Cu] Atualização por classe: | 180113 |
[Lr] Data última revisão:
| 180113 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 171213 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1371/journal.pgen.1007121 |
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