Universität zu Köln

Rieckher, Matthias ORCID: 0000-0002-1945-9474, Markaki, Maria, Princz, Andrea, Schumacher, Bjoern and Tavernarakis, Nektarios ORCID: 0000-0002-5253-1466 (2018). Maintenance of Proteostasis by P Body-Mediated Regulation of eIF4E Availability during Aging in Caenorhabditis elegans. Cell Reports, 25 (1). S. 199 - 218. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

Aging is accompanied by a pervasive collapse of proteostasis, while reducing general protein synthesis promotes longevity across taxa. Here, we show that the eIF4E isoform IFE-2 is increasingly sequestered in mRNA processing (P) bodies during aging and upon stress in Caenorhabditis elegans. Loss of the enhancer of mRNA decapping EDC-3 causes further entrapment of IFE-2 in P bodies and lowers protein synthesis rates in somatic tissues. Animals lacking EDC-3 are long lived and stress resistant, congruent with IFE-2-deficient mutants. Notably, neuron-specific expression of EDC-3 is sufficient to reverse lifespan extension, while sequestration of IFE-2 in neuronal P bodies counteracts age-related neuronal decline. The effects of mRNA decapping deficiency on stress resistance and longevity are orchestrated by a multimodal stress response involving the transcription factor SKN-1, which mediates lifespan extension upon reduced protein synthesis. Our findings elucidate a mechanism of proteostasis control during aging through P body-mediated regulation of protein synthesis in the soma.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rieckher, Matthias UNSPECIFIED orcid.org/0000-0002-1945-9474 UNSPECIFIED Markaki, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Princz, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Tavernarakis, Nektarios UNSPECIFIED orcid.org/0000-0002-5253-1466 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-169678
DOI:	10.1016/j.celrep.2018.09.009
Journal or Publication Title:	Cell Reports
Volume:	25
Number:	1
Page Range:	S. 199 - 218
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EUKARYOTIC MESSENGER-RNAS; C-ELEGANS; LIFE-SPAN; STRESS GRANULES; WILD-TYPE; PROTEIN; EDC3; TRANSLATION; TDP-43; LOCALIZATION Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16967