Presentation/Session Information

Session Information

Session Title: Physiology: Aging and Stress II Session Type: Parallel
Session Location: Carnesale Palisades Ballroom Session Time: Fri, Jun 26 8:30AM - 11:30AM

Presentation Information

Program Number: 76 Presentation Time: 9:06AM - 9:18AM

Presentation Content

mRNA decay interfaces with protein synthesis to modulate stress resistance and longevity in C. elegans.Matthias Rieckher 1,3, Maria Markaki 1, Andrea Princz 1, Nektarios Tavernarakis 1,2. 1)Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Heraklion, Crete, Greece; 2)Medical School, University of Crete, Heraklion, Crete, Greece; 3)The Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), Cologne, Germany

Attenuation of protein synthesis has been demonstrated to increase lifespan across taxa. Recent findings show that activators of mRNA degradation suppress mRNA translation by targeting mRNAs for storage and decapping in cytoplasmic Processing (P) bodies. We hypothesized that storage and degradation of mRNAs in P bodies may regulate physiological processes such as stress responses and ageing via the control of mRNA translation. We observed that somatic P bodies increase in size and number during ageing in C. elegans. IFE-2, an isoform of the translation initiation factor eIF4E, progressively localizes to P bodies upon stress and during ageing. Loss of the P body factor “enhancer of mRNA decapping” EDC-3 promotes longevity and resistance to stress. EDC-3 mutants display reduced protein synthesis in somatic cells. Furthermore, lack of EDC-3 leads to increased P body formation. Notably, longevity and stress resistance in EDC-3-depleted animals is rescued by neuron-specific EDC-3 expression. We find that the transcription factor SKN-1, which also mediates lifespan extension by eIF4E deficiency in somatic C. elegans tissues, is required for the effects of EDC-3 depletion on stress resistance and lifespan. Further, loss of SKN-1 robustly enhances P body formation in EDC-3 mutants. We conclude that upon mRNA decapping impairment, eIF4E becomes sequestered in P bodies, which in turn downregulates general protein synthesis in the soma, thereby increasing organismal lifespan. Our findings indicate a causative role for P bodies in the regulation of stress resistance and ageing.

Please note: Abstract shown here should NOT be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

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