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

Elizabeth Delorme-Axford1, Emma Abernathy2, Nicholas J Lennemann3

  • 1a Life Sciences Institute, University of Michigan , Ann Arbor , MI , USA.

Autophagy
|February 22, 2018
PubMed

Insights

The exoribonuclease Xrn1/XRN1 acts as a negative regulator of autophagy. Its absence enhances autophagy and autophagosome formation in yeast and mammalian cells, revealing its role in post-transcriptional control.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Macroautophagy/autophagy is a crucial catabolic process for cell survival during stress.
  • Dysregulation of autophagy is linked to diseases like cancer and neurodegenerative disorders.
  • Post-transcriptional regulation of autophagy remains incompletely understood.

Purpose of the Study:

  • To investigate the role of the exoribonuclease Xrn1/XRN1 in the post-transcriptional control of autophagy.
  • To determine if Xrn1/XRN1 functions as a regulator of autophagy in yeast and mammalian cells.

Main Methods:

  • Chromosomal deletion of XRN1 in Saccharomyces cerevisiae.
  • siRNA depletion of XRN1 in mammalian cells.
  • Analysis of autophagy-related (ATG) transcript levels and autophagosome formation.
  • Assessment of picornavirus replication in mammalian cells.

Main Results:

  • Deletion or depletion of Xrn1/XRN1 significantly enhances autophagy and autophagosome formation.
  • Loss of Xrn1 leads to increased autophagy-related (ATG) transcript levels, dependent on its ribonuclease activity.
  • Xrn1 expression is modulated by the transcription factor Ash1 in yeast under nutrient-rich conditions.
  • Mammalian cells lacking XRN1 exhibit heightened autophagy and increased picornavirus replication.

Conclusions:

  • Xrn1/XRN1 functions as a negative regulator of autophagy.
  • This study elucidates the role of Xrn1/XRN1 in the post-transcriptional control of autophagy.
  • Xrn1/XRN1 impacts cellular stress responses and viral replication through autophagy modulation.
Keywords:
Ash1Atg8BECN1CRISPRCVBDcp2LC3RNARNA decayautophagosomeautophagy relatedcoxsackievirus BmRNAmacroautophagypicornaviruspoliovirusstressvacuoleyeast

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