An F-Box Protein, Mdm30, Interacts with TREX Subunit Sub2 To Regulate Cellular Abundance Cotranscriptionally in Orchestrating mRNA Export Independently of Splicing and Mitochondrial Function

Mol Cell Biol. 2020 Mar 16;40(7):e00570-19. doi: 10.1128/MCB.00570-19. Print 2020 Mar 16.


Although an F-box protein, Mdm30, is found to regulate ubiquitylation of the Sub2 component of TREX (transcription-export) complex for proteasomal degradation in stimulation of mRNA export, it remains unknown whether such ubiquitin-proteasome system (UPS) regulation of Sub2 occurs cotranscriptionally via its interaction with Mdm30. Further, it is unclear whether impaired UPS regulation of Sub2 in the absence of Mdm30 alters mRNA export via splicing defects of export factors and/or mitochondrial dynamics/function, since Sub2 controls mRNA splicing and Mdm30 regulates mitochondrial aggregation. Here, we show that Mdm30 interacts with Sub2, and temporary shutdown of Mdm30 enhances Sub2's abundance and impairs mRNA export. Likewise, Sub2's abundance is increased following transcriptional inhibition. These results support Mdm30's direct role in regulation of Sub2's cellular abundance in a transcription-dependent manner. Consistently, the chromatin-bound Sub2 level is increased in the absence of Mdm30. Further, we find that Mdm30 does not facilitate splicing of export factors. Moreover, Mdm30 does not have a dramatic effect on mitochondrial respiration/function, and mRNA export occurs in the absence of Fzo1, which is required for mitochondrial dynamics/respiration. Collective results reveal that Mdm30 interacts with Sub2 for proteasomal degradation in a transcription-dependent manner to promote mRNA export independently of splicing or mitochondrial function, thus advancing our understanding of mRNA export.

Keywords: Mdm30; Sub2; gene expression; mRNA export; mRNA splicing; transcription.

Publication types

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

MeSH terms

  • Active Transport, Cell Nucleus / physiology*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • F-Box Proteins / metabolism*
  • GTP Phosphohydrolases / genetics
  • Membrane Proteins / genetics
  • Mitochondria / physiology*
  • Mitochondrial Dynamics / genetics
  • Mitochondrial Proteins / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • RNA Splicing
  • RNA Transport
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic / genetics
  • Ubiquitination


  • F-Box Proteins
  • Mdm30 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Proteins
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Proteasome Endopeptidase Complex
  • Adenosine Triphosphatases
  • FZO1 protein, S cerevisiae
  • GTP Phosphohydrolases
  • RNA-dependent ATPase