期刊
RNA BIOLOGY
卷 13, 期 8, 页码 690-695出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2016.1203503
关键词
cfTERRA; exosomes; inflammation; TAMP (telomere-associated molecular pattern); telomere; TERRA
资金
- NCI NIH HHS [R01 CA140652, P30 CA010815] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA140652, P30CA010815] Funding Source: NIH RePORTER
Telomeric repeats-containing RNA (TERRA) are telomere-derived non-coding RNAs that contribute to telomere function in protecting chromosome ends. We recently identified a cell-free form of TERRA (cfTERRA) enriched in extracellular exosomes. These cfTERRA-containing exosomes stimulate inflammatory cytokines when incubated with immune responsive cells. Here, we report that cfTERRA levels were increased in exosomes during telomere dysfunction induced by the expression of the dominant negative TRF2. The exosomes from these damaged cells also enriched with DNA damage marker H2AX and fragmented telomere repeat DNA. Purified cfTERRA stimulated inflammatory cytokines, but the intact membrane-associated nucleoprotein complexes produced a more robust cytokine activation. Therefore, we propose cfTERRA-containing exosomes transport a telomere-associated molecular pattern (TAMP) and telomere-specific alarmin from dysfunctional telomeres to the extracellular environment to elicit an inflammatory response. Since cfTERRA can be readily detected in human serum it may provide a useful biomarker for the detection of telomere dysfunction in the early stage of cancers and aging-associated inflammatory disease.
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