TRL-1 undergoes phase separation to regulate the reproduction and longevity tradeoff
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ABSTRACT:
PROVIDER: PRJNA763584 | ENA |
REPOSITORIES: ENA
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Project description:The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we demonstrate that an open reading frame (ORF) trl-1 'hidden' within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten lifespan and specifically impair the germline deficiency-induced longevity. The loss of trl-1 abnormally upregulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce lifespan. We show that TRL-1 protein undergoes liquid-liquid phase separation, through which TRL-1 granules recruit vitellogenin mRNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction-longevity tradeoff by optimizing nutrient production for the next generation.
2022-03-22 | GSE184209 | GEO
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Project description:An animal’s ability to effectively capture prey and defend against predators is pivotal to its survival1. A key innovation in many predator-prey interactions is venom, which consists of many toxin proteins that shape its phenotype2. Its unusually direct relationship of gene-toxin-phenotype make it an appealing system for studies at the organismal level 3,4. In this work we use the sea anemone Nematostella vectensis as a model organism as it provides us with the opportunity to test for the first time how toxin-genotypes impact predator-prey interactions. Specifically, we compare a native-population5 and a transgenic line which both have significantly reduced levels of Nv1, the major toxin in adult Nematostella6, to animals with wildtype levels of Nv1. We demonstrate that the transgenic strain phenocopies native anemones lacking Nv1 as they both have impaired ability to defend themselves against grass shrimp, a native predator. Mummichog killifish, unexpectedly are attracted to Nematostella with wildtype-levels of Nv1, highlighting that Nv1 plays a complex role in shaping interspecific-interactions. Finally, we demonstrate an evolutionary tradeoff as the reduction of Nv1 levels causes faster growth and increased reproductive rates compared to Nematostella control lines. Overall, our results experimentally link organism’s venom to its physiology, reproduction and interspecific interactions.
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Project description:Small ubiquitin-like modifiers from the ATG8 family regulate autophagy initiation and progression in mammalian cells. Their interaction with LC3-interacting region (LIR) containing proteins promotes cargo sequestration, phagophore assembly, or even fusion between autophagosomes and lysosomes. Previously, we have shown that RabGAP proteins from the TBC family directly bind to LC3/GABARAP proteins. In the present study, we focus on the function of TBC1D2B. We show that TBC1D2B contains a functional canonical LIR motif and acts at an early stage of autophagy by binding to both LC3/GABARAP proteins and ATG5 conjugation machinery. Subsequently, TBC1D2B is degraded by autophagy. TBC1D2B condensates into liquid droplets upon autophagy induction. Our study suggests that phase separation is an underlying mechanism of TBC1D2B-dependent autophagy induction, which serves as an assembly platform for further cargo sequestration.
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