Universität zu Köln

Efstathiou, Sotirios, Ottens, Franziska ORCID: 0000-0002-0353-2649, Schuetter, Lena-Sophie, Ravanelli, Sonia ORCID: 0000-0002-8511-9339, Charmpilas, Nikolaos, Gutschmidt, Aljona, Le Pen, Jeremie ORCID: 0000-0001-7025-9526, Gehring, Niels H., Miska, Eric A., Boucas, Jorge and Hoppe, Thorsten . ER-associated RNA silencing promotes ER quality control. Nat. Cell Biol.. BERLIN: NATURE PORTFOLIO. ISSN 1476-4679

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Abstract

The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function. Induced by ER stress, ERAS is mediated by the Argonaute protein RDE-1/AGO2, is conserved in mammals and promotes ER-associated RNA turnover. ERAS and ERAD are complementary, as simultaneous inactivation of both quality-control pathways leads to increased ER stress, reduced protein quality control and impaired intestinal integrity. Collectively, our findings indicate that ER homeostasis and organismal health are protected by synergistic functions of ERAS and ERAD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Efstathiou, Sotirios UNSPECIFIED UNSPECIFIED UNSPECIFIED Ottens, Franziska UNSPECIFIED orcid.org/0000-0002-0353-2649 UNSPECIFIED Schuetter, Lena-Sophie UNSPECIFIED UNSPECIFIED UNSPECIFIED Ravanelli, Sonia UNSPECIFIED orcid.org/0000-0002-8511-9339 UNSPECIFIED Charmpilas, Nikolaos UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutschmidt, Aljona UNSPECIFIED UNSPECIFIED UNSPECIFIED Le Pen, Jeremie UNSPECIFIED orcid.org/0000-0001-7025-9526 UNSPECIFIED Gehring, Niels H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Miska, Eric A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boucas, Jorge UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-686214
DOI:	10.1038/s41556-022-01025-4
Journal or Publication Title:	Nat. Cell Biol.
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	1476-4679
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UNFOLDED PROTEIN RESPONSE; MESSENGER-RNA; GENETIC INTERFERENCE; RETICULUM; CLEAVAGE; PATHWAY; STRESS; DECAY; PROTEOSTASIS; DEGRADATION Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68621