SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1

Nicolás G. Simonet; Joshua K. Thackray; Alessandro Ianni; Maria Espinosa-Alcantud; Julia Morales-Sanfrutos; Sarah Hurtado-Bagès; Eduard Sabidó; Marcus Buschbeck; Jay Tischfield; Carolina de la Torre; Manel Esteller; Thomas Braun; Mireia Olivella; Lourdes Serrano; Alejandro Vaquero

doi:10.1126/sciadv.aaz2590

SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1

Nicolás G. Simonet, Joshua K. Thackray, Alessandro Ianni, Maria Espinosa-Alcantud, Julia Morales-Sanfrutos, Sarah Hurtado-Bagès, Eduard Sabidó, Marcus Buschbeck, Jay Tischfield, Carolina de la Torre, Manel Esteller, Thomas Braun, Mireia Olivella, Lourdes Serrano, Alejandro Vaquero

Rutgers, The State University

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5′-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1.1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1.1 axis in glucose homeostasis and aging.

Original language	American English
Article number	aaz2590
Journal	Science advances
Volume	6
Issue number	30
DOIs	https://doi.org/10.1126/sciadv.aaz2590
State	Published - Jul 2020

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Simonet, N. G., Thackray, J. K., Ianni, A., Espinosa-Alcantud, M., Morales-Sanfrutos, J., Hurtado-Bagès, S., Sabidó, E., Buschbeck, M., Tischfield, J., de la Torre, C., Esteller, M., Braun, T., Olivella, M., Serrano, L., & Vaquero, A. (2020). SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1. Science advances, 6(30), Article aaz2590. https://doi.org/10.1126/sciadv.aaz2590

@article{d400c83110f34f9b8d553db457db6e87,

title = "SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1",

abstract = "Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5′-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1.1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1.1 axis in glucose homeostasis and aging.",

author = "Simonet, \{Nicol{\'a}s G.\} and Thackray, \{Joshua K.\} and Alessandro Ianni and Maria Espinosa-Alcantud and Julia Morales-Sanfrutos and Sarah Hurtado-Bag{\`e}s and Eduard Sabid{\'o} and Marcus Buschbeck and Jay Tischfield and \{de la Torre\}, Carolina and Manel Esteller and Thomas Braun and Mireia Olivella and Lourdes Serrano and Alejandro Vaquero",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).",

year = "2020",

month = jul,

doi = "10.1126/sciadv.aaz2590",

language = "American English",

volume = "6",

journal = "Science advances",

issn = "2375-2548",

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Simonet, NG, Thackray, JK, Ianni, A, Espinosa-Alcantud, M, Morales-Sanfrutos, J, Hurtado-Bagès, S, Sabidó, E, Buschbeck, M, Tischfield, J, de la Torre, C, Esteller, M, Braun, T, Olivella, M, Serrano, L & Vaquero, A 2020, 'SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1', Science advances, vol. 6, no. 30, aaz2590. https://doi.org/10.1126/sciadv.aaz2590

TY - JOUR

T1 - SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1

AU - Simonet, Nicolás G.

AU - Thackray, Joshua K.

AU - Ianni, Alessandro

AU - Espinosa-Alcantud, Maria

AU - Morales-Sanfrutos, Julia

AU - Hurtado-Bagès, Sarah

AU - Sabidó, Eduard

AU - Buschbeck, Marcus

AU - Tischfield, Jay

AU - de la Torre, Carolina

AU - Esteller, Manel

AU - Braun, Thomas

AU - Olivella, Mireia

AU - Serrano, Lourdes

AU - Vaquero, Alejandro

N1 - Publisher Copyright: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

PY - 2020/7

Y1 - 2020/7

N2 - Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5′-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1.1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1.1 axis in glucose homeostasis and aging.

AB - Sirtuins are key players of metabolic stress response. Originally described as deacetylases, some sirtuins also exhibit poorly understood mono-adenosine 5′-diphosphate (ADP)-ribosyltransferase (mADPRT) activity. We report that the deacetylase SirT7 is a dual sirtuin, as it also features auto-mADPRT activity. SirT7 mADPRT occurs at a previously undefined active site, and its abrogation alters SirT7 chromatin distribution. We identify an epigenetic pathway by which ADP-ribosyl-SirT7 is recognized by the ADP-ribose reader mH2A1.1 under glucose starvation, inducing SirT7 relocalization to intergenic regions. SirT7 promotes mH2A1 enrichment in a subset of nearby genes, many of them involved in second messenger signaling, resulting in their specific up- or down-regulation. The expression profile of these genes under calorie restriction is consistently abrogated in SirT7-deficient mice, resulting in impaired activation of autophagy. Our work provides a novel perspective on sirtuin duality and suggests a role for SirT7/mH2A1.1 axis in glucose homeostasis and aging.

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U2 - 10.1126/sciadv.aaz2590

DO - 10.1126/sciadv.aaz2590

M3 - Article

C2 - 32832656

SN - 2375-2548

VL - 6

JO - Science advances

JF - Science advances

IS - 30

M1 - aaz2590

ER -

SirT7 auto-ADP-ribosylation regulates glucose starvation response through mH2A1

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