Altered rRNA processing disrupts nuclear RNA homeostasis via competition for the poly(A)-binding protein Nab2

Nucleic Acids Res. 2020 Nov 18;48(20):11675-11694. doi: 10.1093/nar/gkaa964.


RNA-binding proteins (RBPs) are key mediators of RNA metabolism. Whereas some RBPs exhibit narrow transcript specificity, others function broadly across both coding and non-coding RNAs. Here, in Saccharomyces cerevisiae, we demonstrate that changes in RBP availability caused by disruptions to distinct cellular processes promote a common global breakdown in RNA metabolism and nuclear RNA homeostasis. Our data shows that stabilization of aberrant ribosomal RNA (rRNA) precursors in an enp1-1 mutant causes phenotypes similar to RNA exosome mutants due to nucleolar sequestration of the poly(A)-binding protein (PABP) Nab2. Decreased nuclear PABP availability is accompanied by genome-wide changes in RNA metabolism, including increased pervasive transcripts levels and snoRNA processing defects. These phenotypes are mitigated by overexpression of PABPs, inhibition of rDNA transcription, or alterations in TRAMP activity. Our results highlight the need for cells to maintain poly(A)-RNA levels in balance with PABPs and other RBPs with mutable substrate specificity across nucleoplasmic and nucleolar RNA processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Exosome Multienzyme Ribonuclease Complex / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Homeostasis
  • Mutation
  • Nuclear Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Polyadenylation
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA, Ribosomal / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcriptome


  • CSL4 protein, S cerevisiae
  • ENP1 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • NAB2 protein, S cerevisiae
  • Nuclear Proteins
  • Nucleocytoplasmic Transport Proteins
  • RNA Precursors
  • RNA, Ribosomal
  • RNA-Binding Proteins
  • SRM1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Exosome Multienzyme Ribonuclease Complex