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The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy.

Publication ,  Journal Article
Delorme-Axford, E; Abernathy, E; Lennemann, NJ; Bernard, A; Ariosa, A; Coyne, CB; Kirkegaard, K; Klionsky, DJ
Published in: Autophagy
2018

Macroautophagy/autophagy is a conserved catabolic process that promotes survival during stress. Autophagic dysfunction is associated with pathologies such as cancer and neurodegenerative diseases. Thus, autophagy must be strictly modulated at multiple levels (transcriptional, post-transcriptional, translational and post-translational) to prevent deregulation. Relatively little is known about the post-transcriptional control of autophagy. Here we report that the exoribonuclease Xrn1/XRN1 functions as a negative autophagy factor in the yeast Saccharomyces cerevisiae and in mammalian cells. In yeast, chromosomal deletion of XRN1 enhances autophagy and the frequency of autophagosome formation. Loss of Xrn1 results in the upregulation of autophagy-related (ATG) transcripts under nutrient-replete conditions, and this effect is dependent on the ribonuclease activity of Xrn1. Xrn1 expression is regulated by the yeast transcription factor Ash1 in rich conditions. In mammalian cells, siRNA depletion of XRN1 enhances autophagy and the replication of 2 picornaviruses. This work provides insight into the role of the RNA decay factor Xrn1/XRN1 as a post-transcriptional regulator of autophagy.

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Published In

Autophagy

DOI

EISSN

1554-8635

Publication Date

2018

Volume

14

Issue

5

Start / End Page

898 / 912

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • RNA, Messenger
  • Microtubule-Associated Proteins
  • Humans
  • Hela Cells
  • HeLa Cells
  • Exoribonucleases
 

Citation

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Delorme-Axford, E., Abernathy, E., Lennemann, N. J., Bernard, A., Ariosa, A., Coyne, C. B., … Klionsky, D. J. (2018). The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy. Autophagy, 14(5), 898–912. https://doi.org/10.1080/15548627.2018.1441648
Delorme-Axford, Elizabeth, Emma Abernathy, Nicholas J. Lennemann, Amélie Bernard, Aileen Ariosa, Carolyn B. Coyne, Karla Kirkegaard, and Daniel J. Klionsky. “The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy.Autophagy 14, no. 5 (2018): 898–912. https://doi.org/10.1080/15548627.2018.1441648.
Delorme-Axford E, Abernathy E, Lennemann NJ, Bernard A, Ariosa A, Coyne CB, et al. The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy. Autophagy. 2018;14(5):898–912.
Delorme-Axford, Elizabeth, et al. “The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy.Autophagy, vol. 14, no. 5, 2018, pp. 898–912. Pubmed, doi:10.1080/15548627.2018.1441648.
Delorme-Axford E, Abernathy E, Lennemann NJ, Bernard A, Ariosa A, Coyne CB, Kirkegaard K, Klionsky DJ. The exoribonuclease Xrn1 is a post-transcriptional negative regulator of autophagy. Autophagy. 2018;14(5):898–912.

Published In

Autophagy

DOI

EISSN

1554-8635

Publication Date

2018

Volume

14

Issue

5

Start / End Page

898 / 912

Location

United States

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Repressor Proteins
  • RNA, Messenger
  • Microtubule-Associated Proteins
  • Humans
  • Hela Cells
  • HeLa Cells
  • Exoribonucleases