Universität zu Köln

Finger, Fabian ORCID: 0000-0002-0763-6250, Ottens, Franziska, Springhorn, Alexander, Drexel, Tanja, Proksch, Lucie, Metz, Sophia ORCID: 0000-0001-5871-9892, Cochella, Luisa ORCID: 0000-0003-4018-7722 and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2019). Olfaction regulates organismal proteostasis and longevity via microRNA-dependent signalling. Nat. Metab., 1 (3). S. 350 - 360. LONDON: NATURE PUBLISHING GROUP. ISSN 2522-5812

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Abstract

The maintenance of proteostasis is crucial for any organism to survive and reproduce in an ever-changing environment, but its efficiency declines with age(1). Post-transcriptional regulators such as micrRNAs (miRNAs) control protein translation of target mRNAs, with major consequences for development, physiology and longevity(2,3). Here we show that food odour stimulates organismal proteostasis and promotes longevity in Caenorhabditis elegans through miR-71-mediated inhibition of tir-1 mRNA stability in olfactory AWC neurons. Screening a collection of miRNAs that control ageing(3), we found that the miRNA miR-71 regulates lifespan and promotes ubiquitin-dependent protein turnover, particularly in the intestine. We show that miR-71 directly inhibits the Toll-receptor-domain protein TIR-1 in AWC olfactory neurons and that disruption of miR-71-tir-1 or loss of AWC olfactory neurons eliminates the influence of food source on proteostasis. miR-71-mediated regulation of TIR-1 controls chemotactic behaviour and is regulated by odour. Thus, odour perception influences cell-type-specific miRNA-target interaction, thereby regulating organismal proteostasis and longevity. We anticipate that the proposed mechanism of food perception will stimulate further research on neuroendocrine brain-to-gut communication and may open the possibility for therapeutic interventions to improve proteostasis and organismal health via the sense of smell, with potential implications for obesity, diabetes and ageing.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Finger, Fabian UNSPECIFIED orcid.org/0000-0002-0763-6250 UNSPECIFIED Ottens, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Springhorn, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Drexel, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Proksch, Lucie UNSPECIFIED UNSPECIFIED UNSPECIFIED Metz, Sophia UNSPECIFIED orcid.org/0000-0001-5871-9892 UNSPECIFIED Cochella, Luisa UNSPECIFIED orcid.org/0000-0003-4018-7722 UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-154362
DOI:	10.1038/s42255-019-0033-z
Journal or Publication Title:	Nat. Metab.
Volume:	1
Number:	3
Page Range:	S. 350 - 360
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2522-5812
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; C. ELEGANS; PROTEIN; NEURONS; SARM1; CHEMOTAXIS; RESISTANCE; RESPONSES; BEHAVIOR; PATHWAY Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15436