A STAT3 protein complex required for mitochondrial mRNA stability and cancer

Cell Rep. 2023 Sep 26;42(9):113033. doi: 10.1016/j.celrep.2023.113033. Epub 2023 Sep 12.


Signal transducer and activator of transcription 3 (STAT3) is a potent transcription factor necessary for life whose activity is corrupted in diverse diseases, including cancer. STAT3 biology was presumed to be entirely dependent on its activity as a transcription factor until the discovery of a mitochondrial pool of STAT3, which is necessary for normal tissue function and tumorigenesis. However, the mechanism of this mitochondrial activity remained elusive. This study uses immunoprecipitation and mass spectrometry to identify a complex containing STAT3, leucine-rich pentatricopeptide repeat containing (LRPPRC), and SRA stem-loop-interacting RNA-binding protein (SLIRP) that is required for the stability of mature mitochondrially encoded mRNAs and transport to the mitochondrial ribosome. Moreover, we show that this complex is enriched in patients with lung adenocarcinoma and that its deletion inhibits the growth of lung cancer in vivo, providing therapeutic opportunities through the specific targeting of the mitochondrial activity of STAT3.

Keywords: CP: Cancer; CP: Molecular biology; LRPPRC; SLIRP; STAT3; lung adenocarcinoma; mRNA stability; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / metabolism
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Mitochondria / metabolism
  • RNA Stability / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism


  • STAT3 Transcription Factor
  • STAT3 protein, human
  • SLIRP protein, human
  • RNA-Binding Proteins