SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation.

Abstract

Synchronisation of translation rates between the mitochondria and their cellular host is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translation uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, the compensating mechanisms in place in the mitochondria remain elusive. Here we show that the malignant lncRNA SAMMSON promotes a balanced increase in rRNA maturation and protein synthesis in the cytosol and mitochondria by modulating the localisation of CARF, an RNA-binding protein sequestering XRN2 in the nucleoplasm and limiting nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favouring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. This data highlights how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth.