Report A STAT3 protein complex required for mitochondrial mRNA stability and cancer

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 mito-chondrially 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.

Automated summary

This study identifies a complex consisting of STAT3, LRPPRC, and SLIRP, which is required for the stability and transport of mature mito-chondrially encoded mRNAs to the mitochondrial ribosome. The complex is enriched in patients with lung adenocarcinoma and its deletion inhibits the growth of lung cancer.