Bulk RNA degradation by nitrogen starvation-induced autophagy in yeast

EMBO J. 2015 Jan 13;34(2):154-68. doi: 10.15252/embj.201489083. Epub 2014 Dec 2.

Abstract

Autophagy is a catabolic process conserved among eukaryotes. Under nutrient starvation, a portion of the cytoplasm is non-selectively sequestered into autophagosomes. Consequently, ribosomes are delivered to the vacuole/lysosome for destruction, but the precise mechanism of autophagic RNA degradation and its physiological implications for cellular metabolism remain unknown. We characterized autophagy-dependent RNA catabolism using a combination of metabolome and molecular biological analyses in yeast. RNA delivered to the vacuole was processed by Rny1, a T2-type ribonuclease, generating 3'-NMPs that were immediately converted to nucleosides by the vacuolar non-specific phosphatase Pho8. In the cytoplasm, these nucleosides were broken down by the nucleosidases Pnp1 and Urh1. Most of the resultant bases were not re-assimilated, but excreted from the cell. Bulk non-selective autophagy causes drastic perturbation of metabolism, which must be minimized to maintain intracellular homeostasis.

Keywords: RNA degradation; autophagy; metabolome analysis; ribosome; vacuole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Autophagy*
  • Autophagy-Related Proteins
  • Blotting, Western
  • Chromatography, Liquid
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Mass Spectrometry
  • Metabolome
  • Microscopy, Fluorescence
  • Nitrogen / metabolism*
  • RNA Stability*
  • Ribonucleases / genetics
  • Ribonucleases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Starvation*
  • Vacuoles / metabolism

Substances

  • ATG2 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Saccharomyces cerevisiae Proteins
  • Ribonucleases
  • Rny1 protein, S cerevisiae
  • Alkaline Phosphatase
  • PHO8 protein, S cerevisiae
  • Endopeptidases
  • Bre5 protein, S cerevisiae
  • UBP3 protein, S cerevisiae
  • Nitrogen