Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

Camilla Nehammer; Patrick Ejlerskov; Sandeep Gopal; Ava Handley; Leelee Ng; Pedro Moreira; Huikyong Lee; Shohreh Issazadeh-Navikas; David C Rubinsztein; Roger Pocock

doi:10.7554/eLife.49930

Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

Camilla Nehammer, Patrick Ejlerskov, Sandeep Gopal, Ava Handley, Leelee Ng, Pedro Moreira, Huikyong Lee, Shohreh Issazadeh-Navikas, David C Rubinsztein, Roger Pocock

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

Abstract

Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.

Original language	English
Article number	e49930
Journal	eLife
Volume	8
DOIs	https://doi.org/10.7554/eLife.49930
Publication status	Published - 2019 Dec 4
Externally published	Yes

Bibliographical note

Subject classification (UKÄ)

Cell and Molecular Biology
Endocrinology and Diabetes
Biological Sciences

Free keywords

3' Untranslated Regions/genetics
Animals
Autophagy
Base Sequence
Caenorhabditis elegans/metabolism
Caenorhabditis elegans Proteins/genetics
GTPase-Activating Proteins/genetics
HeLa Cells
Humans
Huntingtin Protein/metabolism
Interferon-beta/metabolism
Mice
MicroRNAs/metabolism
Mutant Proteins/metabolism
Peptides/metabolism
Protein Aggregates
RNA, Messenger/genetics
rab GTP-Binding Proteins/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.7554/eLife.49930Licence: CC BY

Cite this

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title = "Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy",

abstract = "Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.",

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author = "Camilla Nehammer and Patrick Ejlerskov and Sandeep Gopal and Ava Handley and Leelee Ng and Pedro Moreira and Huikyong Lee and Shohreh Issazadeh-Navikas and Rubinsztein, {David C} and Roger Pocock",

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language = "English",

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journal = "eLife",

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AU - Nehammer, Camilla

AU - Ejlerskov, Patrick

AU - Gopal, Sandeep

AU - Handley, Ava

AU - Ng, Leelee

AU - Moreira, Pedro

AU - Lee, Huikyong

AU - Issazadeh-Navikas, Shohreh

AU - Rubinsztein, David C

AU - Pocock, Roger

PY - 2019/12/4

Y1 - 2019/12/4

N2 - Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.

AB - Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.

KW - 3' Untranslated Regions/genetics

KW - Animals

KW - Autophagy

KW - Base Sequence

KW - Caenorhabditis elegans/metabolism

KW - Caenorhabditis elegans Proteins/genetics

KW - GTPase-Activating Proteins/genetics

KW - HeLa Cells

KW - Humans

KW - Huntingtin Protein/metabolism

KW - Interferon-beta/metabolism

KW - Mice

KW - MicroRNAs/metabolism

KW - Mutant Proteins/metabolism

KW - Peptides/metabolism

KW - Protein Aggregates

KW - RNA, Messenger/genetics

KW - rab GTP-Binding Proteins/metabolism

U2 - 10.7554/eLife.49930

DO - 10.7554/eLife.49930

M3 - Article

C2 - 31799933

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

M1 - e49930

ER -

Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

Abstract

Bibliographical note

Subject classification (UKÄ)

Free keywords

UN SDGs

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