Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy
Nehammer, Camilla ; Ejlerskov, Patrick ; Gopal, Sandeep LU
; Handley, Ava
; Ng, Leelee
; Moreira, Pedro
; Lee, Huikyong
; Issazadeh-Navikas, Shohreh
; Rubinsztein, David C
and Pocock, Roger
(2019)
In eLife
8.
- 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)... (More)
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.
(Less)
- author
- Nehammer, Camilla
; Ejlerskov, Patrick
; Gopal, Sandeep
LU
; Handley, Ava
; Ng, Leelee
; Moreira, Pedro
; Lee, Huikyong
; Issazadeh-Navikas, Shohreh
; Rubinsztein, David C
and Pocock, Roger
- publishing date
- 2019-12-04
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- in
- eLife
- volume
- 8
- article number
- e49930
- publisher
- eLife Sciences Publications
- external identifiers
-
- pmid:31799933
- scopus:85076544968
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.49930
- language
- English
- LU publication?
- no
- additional info
- © 2019, Nehammer et al.
- id
- 2bc70396-6a6e-49bd-8c04-5c2378c7cc18
- date added to LUP
- 2021-10-25 12:59:10
- date last changed
- 2024-06-15 18:54:39
@article{2bc70396-6a6e-49bd-8c04-5c2378c7cc18,
abstract = {{<p>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 <i style="box-sizing: border-box; color: rgb(33, 33, 33); font-family: "Noto Serif", serif; font-size: 16px;">Caenorhabditis elegans</i> 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.</p>}},
author = {{Nehammer, Camilla and Ejlerskov, Patrick and Gopal, Sandeep and Handley, Ava and Ng, Leelee and Moreira, Pedro and Lee, Huikyong and Issazadeh-Navikas, Shohreh and Rubinsztein, David C and Pocock, Roger}},
issn = {{2050-084X}},
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}},
language = {{eng}},
month = {{12}},
publisher = {{eLife Sciences Publications}},
series = {{eLife}},
title = {{Interferon-β-induced miR-1 alleviates toxic protein accumulation by controlling autophagy}},
url = {{http://dx.doi.org/10.7554/eLife.49930}},
doi = {{10.7554/eLife.49930}},
volume = {{8}},
year = {{2019}},
}