TANGO6 coordinates transcription and translation through nucleocytoplasmic partitioning

Abstract

Coordinated RNA and protein synthesis is fundamental to cell function and survival. Here, we show that TANGO6, a nucleocytoplasmic RNA binding protein, is an integral component of the proteostasis control axis, regulating both transcription and translation. In the nucleus, TANGO6 is recruited to gene promoters alongside RNA polymerase II, where it controls the transcriptional activation of essential genes, including those required for G1-S cell cycle progression and cell differentiation. Cytoplasmic TANGO6 associates with polysomes to promote protein synthesis. Under stress conditions, the organization of TANGO6 changes; notably, heat stress triggers its translocation to the nucleus, thereby depleting its cytoplasmic pool. Thus, TANGO6 assists in both transcriptional and translation reprogramming to support cell survival. Overall, the nucleocytoplasmic shuttling of TANGO6 is a central mechanism for controlling the cellular proteome, establishing its essential role in cell viability from homeostasis to stress adaptation.