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Hajikazemi, M.

Publications and source records attributed to Hajikazemi, M..

2 recordsLinked to original sources

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.

molecular biology↗

cGAS/STING-DEPENDENT SENSING OF ENDOGENOUS RNA

Defects in nucleic acid metabolizing enzymes lead to spontaneous but selective activation of either cGAS/STING or RIG-like receptor (RLR) signaling, causing a pathogenic type I interferon response and inflammatory diseases. In these pathophysiological conditions, cGAS-driven IFN production is linked to spontaneous DNA damage. Physiological, or tonic, IFN signaling on the other hand is essential to functionally prime nucleic acid sensing pathways. Here we show that low-level chronic DNA damage in mice lacking the Aicardi-Goutieres syndrome gene SAMHD1 reduced tumor-free survival when crossed to a p53-deficient, but not to DNA mismatch repair-deficient background. Increased DNA damage did not result in higher levels of type I interferon. Instead, we found that the chronic interferon response in SAMHD1-deficient mice was driven by the MDA5/MAVS pathway but required functional priming through the cGAS/STING pathway. Our work positions cGAS/STING upstream of tonic IFN signaling and highlights an important role of the pathway in physiological and pathophysiological innate immune priming. SummaryLoss of the dNTPase and DNA repair enzyme SAMHD1 is associated with cancer and causes systemic autoimmunity. We show transformation-promoting spontaneous DNA damage and MDA5-driven but cGAS/STING-dependent chronic type I interferon production in SAMHD1-deficient mice.

immunology↗