A STAT3 protein complex required for mitochondrial mRNA stability and cancer
- Publisher:
- Elsevier
- Publication Type:
- Journal Article
- Citation:
- Cell Reports, 2023, 42, (9), pp. 113033
- Issue Date:
- 2023-09
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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
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