title: Ubiquitylation by the Ltn1 E3 ligase protects 60S ribosomes from starvation-induced selective autophagy.
abstract: Autophagy, the process by which proteins or organelles are engulfed by autophagosomes and delivered for vacuolar/lysosomal degradation, is induced to ensure survival under starvation and other stresses. A selective autophagic pathway for 60S ribosomal subunits elicited by nitrogen starvation in yeast-ribophagy-was recently described and requires the Ubp3-Bre5 deubiquitylating enzyme. This discovery implied that an E3 ligases act upstream, whether inhibiting the process or providing an initial required signal. In this paper, we show that Ltn1/Rkr1, a 60S ribosome-associated E3 implicated in translational surveillance, acts as an inhibitor of 60S ribosomal subunit ribophagy and is antagonized by Ubp3. The ribosomal protein Rpl25 is a relevant target. Its ubiquitylation is Ltn1 dependent and Ubp3 reversed, and mutation of its ubiquitylation site rendered ribophagy less dependent on Ubp3. Consistently, the expression of Ltn1-but not Ubp3-rapidly decreased after starvation, presumably to allow ribophagy to proceed. Thus, Ltn1 and Ubp3-Bre5 likely contribute to adapt ribophagy activity to both nutrient supply and protein translation.
authors.affiliation: Institut Jacques Monod, University Paris Diderot, Sorbonne Paris Cité, and Centre National de la Recherche Scientifique Unité Mixte de Recherche 7592, 75205 Paris, Cedex 13, France.
authors.forename: Batool
authors.initials: B
authors.lastname: Ossareh-Nazari
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Niño
authors.forename: Mario H
authors.initials: MH
authors.lastname: Bengtson
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Claudio A P
authors.initials: CA
authors.lastname: Joazeiro
authors.forename: Catherine
authors.initials: C
authors.lastname: Dargemont
mesh_terms: D001343:Autophagy; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D004794:Enzyme Repression; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D009584:Nitrogen / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D054683:Ribosome Subunits, Large, Eukaryotic / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C031127:ribosomal protein L25; C552998:Ltn1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C101111:UBP3 protein, S cerevisiae; D009584:Nitrogen