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

5 Citations (Scopus)

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
Journal	eLife
Volume	8
ISSN	2050-084X
DOIs	https://doi.org/10.7554/elife.49930
Publication status	Published - Dec 2019

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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.",

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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TY - JOUR

T1 - Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy

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

Y1 - 2019/12

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.

U2 - 10.7554/elife.49930

DO - 10.7554/elife.49930

M3 - Journal article

C2 - 31799933

SN - 2050-084X

VL - 8

JO - eLife

JF - eLife

ER -

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

Abstract

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