miR-4734 conditionally suppresses ER stress-associated proinflammatory responses

Dan Michael; Ester Feldmesser; Chagay Gonen; Noa Furth; Alexander Maman; Ori Heyman; Amir Argoetti; Adin Tofield; Amichai Baichman-Kass; Aviyah Ben-Dov; Dan Benbenisti; Nadav Hen; Ron Rotkopf; Federica Ganci; Giovanni Blandino; Igor Ulitsky; Moshe Oren

doi:10.1002/1873-3468.14548

miR-4734 conditionally suppresses ER stress-associated proinflammatory responses

Dan Michael, Ester Feldmesser, Chagay Gonen, Noa Furth, Alexander Maman, Ori Heyman, Amir Argoetti, Adin Tofield, Amichai Baichman-Kass, Aviyah Ben-Dov, Dan Benbenisti, Nadav Hen, Ron Rotkopf, Federica Ganci, Giovanni Blandino, Igor Ulitsky, Moshe Oren

Weizmann Institute of Science, Tel Aviv University

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

Abstract

Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of the transcriptional activator NF-kappa-B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR-4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR-4734, underscoring the importance of this direct targeting. As the effects of miR-4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress-induced pathologies.

Original language	English
Pages (from-to)	1233-1245
Number of pages	13
Journal	FEBS Letters
Volume	597
Issue number	9
DOIs	https://doi.org/10.1002/1873-3468.14548
State	Published - 1 May 2023

Keywords

ATF4
ER stress
IRE1a
NFKBIZ
inflammation
miR-4734

All Science Journal Classification (ASJC) codes

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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Michael, D., Feldmesser, E., Gonen, C., Furth, N., Maman, A., Heyman, O., Argoetti, A., Tofield, A., Baichman-Kass, A., Ben-Dov, A., Benbenisti, D., Hen, N., Rotkopf, R., Ganci, F., Blandino, G., Ulitsky, I., & Oren, M. (2023). miR-4734 conditionally suppresses ER stress-associated proinflammatory responses. FEBS Letters, 597(9), 1233-1245. https://doi.org/10.1002/1873-3468.14548

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title = "miR-4734 conditionally suppresses ER stress-associated proinflammatory responses",

abstract = "Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of the transcriptional activator NF-kappa-B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR-4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR-4734, underscoring the importance of this direct targeting. As the effects of miR-4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress-induced pathologies.",

keywords = "ATF4, ER stress, IRE1a, NFKBIZ, inflammation, miR-4734",

author = "Dan Michael and Ester Feldmesser and Chagay Gonen and Noa Furth and Alexander Maman and Ori Heyman and Amir Argoetti and Adin Tofield and Amichai Baichman-Kass and Aviyah Ben-Dov and Dan Benbenisti and Nadav Hen and Ron Rotkopf and Federica Ganci and Giovanni Blandino and Igor Ulitsky and Moshe Oren",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors. FEBS Letters published by John Wiley \& Sons Ltd on behalf of Federation of European Biochemical Societies.",

year = "2023",

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doi = "10.1002/1873-3468.14548",

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Michael, D, Feldmesser, E, Gonen, C, Furth, N, Maman, A, Heyman, O, Argoetti, A, Tofield, A, Baichman-Kass, A, Ben-Dov, A, Benbenisti, D, Hen, N, Rotkopf, R, Ganci, F, Blandino, G, Ulitsky, I & Oren, M 2023, 'miR-4734 conditionally suppresses ER stress-associated proinflammatory responses', FEBS Letters, vol. 597, no. 9, pp. 1233-1245. https://doi.org/10.1002/1873-3468.14548

TY - JOUR

T1 - miR-4734 conditionally suppresses ER stress-associated proinflammatory responses

AU - Michael, Dan

AU - Feldmesser, Ester

AU - Gonen, Chagay

AU - Furth, Noa

AU - Maman, Alexander

AU - Heyman, Ori

AU - Argoetti, Amir

AU - Tofield, Adin

AU - Baichman-Kass, Amichai

AU - Ben-Dov, Aviyah

AU - Benbenisti, Dan

AU - Hen, Nadav

AU - Rotkopf, Ron

AU - Ganci, Federica

AU - Blandino, Giovanni

AU - Ulitsky, Igor

AU - Oren, Moshe

PY - 2023/5/1

Y1 - 2023/5/1

N2 - Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of the transcriptional activator NF-kappa-B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR-4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR-4734, underscoring the importance of this direct targeting. As the effects of miR-4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress-induced pathologies.

AB - Prolonged metabolic stress can lead to severe pathologies. In metabolically challenged primary fibroblasts, we assigned a novel role for the poorly characterized miR-4734 in restricting ATF4 and IRE1-mediated upregulation of a set of proinflammatory cytokines and endoplasmic reticulum stress-associated genes. Conversely, inhibition of this miRNA augmented the expression of those genes. Mechanistically, miR-4734 was found to restrict the expression of the transcriptional activator NF-kappa-B inhibitor zeta (NFKBIZ), which is required for optimal expression of the proinflammatory genes and whose mRNA is targeted directly by miR-4734. Concordantly, overexpression of NFKBIZ compromised the effects of miR-4734, underscoring the importance of this direct targeting. As the effects of miR-4734 were evident under stress but not under basal conditions, it may possess therapeutic utility towards alleviating stress-induced pathologies.

KW - ATF4

KW - ER stress

KW - IRE1a

KW - NFKBIZ

KW - inflammation

KW - miR-4734

UR - http://www.scopus.com/inward/record.url?scp=85144093686&partnerID=8YFLogxK

U2 - 10.1002/1873-3468.14548

DO - 10.1002/1873-3468.14548

M3 - مقالة

C2 - 36445168

SN - 0014-5793

VL - 597

SP - 1233

EP - 1245

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

miR-4734 conditionally suppresses ER stress-associated proinflammatory responses

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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