Telomeric lncRNA TERRA localizes to stress granules in human ALT cells

TERRA, the lncRNA derived from the ends of chromosomes, has a number of well-described nuclear roles including telomere maintenance and homeostasis. A growing body of evidence now points at its role in human cells outside of nucleus--it has been found to be a component of extracellular vesicles, a player in inflammation signalling and its capacity for translation has been shown. In this work, using a combination of sensitive microscopy methods, cellular fractionation, proteomics and transcriptome analysis, we demonstrate directly for the first time that TERRA is present in the cytoplasm of human telomerase-negative cells, especially upon various stress stimuli, and that it associates with stress granules. Confirming the presence of TERRA in the cytoplasm, our work fills an important gap in the field, and contributes to the discussion about the role of TERRA as a transcript involved in nucleo-cytoplasmic stress communication.