Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate

Julie Candiracci; Valerie Migeot; Yok-Hian Chionh; Fanelie Bauer; Thomas Brochier; Brandon Russell; Kazuhiro Shiozaki; Peter Dedon; Damien Hermand

doi:10.1126/sciadv.aav0184

Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate

Julie Candiracci, Valerie Migeot, Yok-Hian Chionh, Fanelie Bauer, Thomas Brochier, Brandon Russell, Kazuhiro Shiozaki, Peter Dedon, Damien Hermand

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Abstract

Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growth from cell division to generate small, round-shaped cells that are competent for sexual differentiation. The TORC1 (TOR complex 1) and TORC2 complexes exert opposite controls on cell growth and cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA (tRNA) modifications by Elongator are critical for this regulation by promoting the translation of both key components of TORC2 and repressors of TORC1. We further identified the TORC2 pathway as an activator of Elongator by down-regulating a Gsk3 (glycogen synthase kinase 3)-dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex (TORC) signaling and tRNA modification by Elongator to enforce the advancement of mitosis that precedes cell differentiation.

Original language	English
Article number	eaav0184
Pages (from-to)	eaav0184
Number of pages	13
Journal	Science Advances
Volume	5
Issue number	6
DOIs	https://doi.org/10.1126/sciadv.aav0184
Publication status	Published - Jun 2019

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title = "Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate",

abstract = "Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growth from cell division to generate small, round-shaped cells that are competent for sexual differentiation. The TORC1 (TOR complex 1) and TORC2 complexes exert opposite controls on cell growth and cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA (tRNA) modifications by Elongator are critical for this regulation by promoting the translation of both key components of TORC2 and repressors of TORC1. We further identified the TORC2 pathway as an activator of Elongator by down-regulating a Gsk3 (glycogen synthase kinase 3)-dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex (TORC) signaling and tRNA modification by Elongator to enforce the advancement of mitosis that precedes cell differentiation.",

author = "Julie Candiracci and Valerie Migeot and Yok-Hian Chionh and Fanelie Bauer and Thomas Brochier and Brandon Russell and Kazuhiro Shiozaki and Peter Dedon and Damien Hermand",

note = "Funding Information: We thank S. Oliferenko, Y. Gu, J. Petersen, R. Weisman, D. Helmlinger, J. B{\"a}hler, S. Moreno, and F. Tamanoi for reagents and strains. This work was supported by grants MIS F.4523.11, PDR T.0012.14, and CDR J.0066.16 (to D.H); grant NIH ES026856 (to P.D.); and the National Research Foundation of Singapore under the Singapore-MIT Alliance for Research and Technology (to P.D.). J.C. was supported by a FRIA fellowship. Publisher Copyright: Copyright {\textcopyright} 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

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AU - Candiracci, Julie

AU - Migeot, Valerie

AU - Chionh, Yok-Hian

AU - Bauer, Fanelie

AU - Brochier, Thomas

AU - Russell, Brandon

AU - Shiozaki, Kazuhiro

AU - Dedon, Peter

AU - Hermand, Damien

N1 - Funding Information: We thank S. Oliferenko, Y. Gu, J. Petersen, R. Weisman, D. Helmlinger, J. Bähler, S. Moreno, and F. Tamanoi for reagents and strains. This work was supported by grants MIS F.4523.11, PDR T.0012.14, and CDR J.0066.16 (to D.H); grant NIH ES026856 (to P.D.); and the National Research Foundation of Singapore under the Singapore-MIT Alliance for Research and Technology (to P.D.). J.C. was supported by a FRIA fellowship. Publisher Copyright: Copyright © 2019 The Authors Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/6

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N2 - Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growth from cell division to generate small, round-shaped cells that are competent for sexual differentiation. The TORC1 (TOR complex 1) and TORC2 complexes exert opposite controls on cell growth and cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA (tRNA) modifications by Elongator are critical for this regulation by promoting the translation of both key components of TORC2 and repressors of TORC1. We further identified the TORC2 pathway as an activator of Elongator by down-regulating a Gsk3 (glycogen synthase kinase 3)-dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex (TORC) signaling and tRNA modification by Elongator to enforce the advancement of mitosis that precedes cell differentiation.

AB - Nutrient availability has a profound impact on cell fate. Upon nitrogen starvation, wild-type fission yeast cells uncouple cell growth from cell division to generate small, round-shaped cells that are competent for sexual differentiation. The TORC1 (TOR complex 1) and TORC2 complexes exert opposite controls on cell growth and cell differentiation, but little is known about how their activity is coordinated. We show that transfer RNA (tRNA) modifications by Elongator are critical for this regulation by promoting the translation of both key components of TORC2 and repressors of TORC1. We further identified the TORC2 pathway as an activator of Elongator by down-regulating a Gsk3 (glycogen synthase kinase 3)-dependent inhibitory phosphorylation of Elongator. Therefore, a feedback control is operating between TOR complex (TORC) signaling and tRNA modification by Elongator to enforce the advancement of mitosis that precedes cell differentiation.

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Reciprocal regulation of TORC signaling and tRNA modifications by Elongator enforces nutrient-dependent cell fate

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