SAMMSON promotes cancer cell fitness by enhancing concertedly mitochondrial and cytosolic protein synthesis

Mitochondria and its cellular host have evolved an intricate series of bi-directional communication mechanisms ensuring coordination of key biological processes. Syn-chronisation of translation rates between the two compartments is particularly critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to trans-lation uncoupling. Although mitochondria are attractive anti-cancer therapeutic targets, the mechanisms underlying coordinated protein synthesis remain elusive. Here we show that the malignant lncRNA SAMMSON modulates the activity of CARF, an RNA-binding protein sequestering XRN2 in the nucleoplasm and limiting nucleolar rRNA maturation. SAMMSON concomitantly releases XRN2 from CARF-binding and favour the formation of an aberrant RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNA. By re-directing CARF protein-binding affinities, SAMMSON promotes a balanced increase in rRNA maturation and protein synthesis in the cytosol and mitochondria. These data highlight how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct/distant cellular compartments to promote cell growth.