The Pat1-Lsm Complex Stabilizes ATG mRNA during Nitrogen Starvation-Induced Autophagy

Mol Cell. 2019 Jan 17;73(2):314-324.e4. doi: 10.1016/j.molcel.2018.11.002. Epub 2018 Dec 6.

Abstract

Macroautophagy/autophagy is a key catabolic recycling pathway that requires fine-tuned regulation to prevent pathologies and preserve homeostasis. Here, we report a new post-transcriptional pathway regulating autophagy involving the Pat1-Lsm (Lsm1 to Lsm7) mRNA-binding complex. Under nitrogen-starvation conditions, Pat1-Lsm binds a specific subset of autophagy-related (ATG) transcripts and prevents their 3' to 5' degradation by the exosome complex, leading to ATG mRNA stabilization and accumulation. This process is regulated through Pat1 dephosphorylation, is necessary for the efficient expression of specific Atg proteins, and is required for robust autophagy induction during nitrogen starvation. To the best of our knowledge, this work presents the first example of ATG transcript regulation via 3' binding factors and exosomal degradation.

Keywords: 3′-5′ degradation; Lsm1; Mrt1; PATL1; exosome; mRNA decay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • 3' Untranslated Regions
  • Autophagy*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Binding Sites
  • Gene Expression Regulation, Fungal
  • Humans
  • Jurkat Cells
  • Multiprotein Complexes
  • Nitrogen / deficiency*
  • Phosphorylation
  • Protein Binding
  • RNA Cap-Binding Proteins / genetics
  • RNA Cap-Binding Proteins / metabolism*
  • RNA Stability*
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • Autophagy-Related Proteins
  • Multiprotein Complexes
  • PAT1 protein, S cerevisiae
  • RNA Cap-Binding Proteins
  • RNA, Fungal
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Nitrogen