Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Abstract

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERCis imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53levels respond to mito- chondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53functions downstream of mitochondria as a signal of mitochon- drial functions. Here, we show that cytosolic TERC-53plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53levels affects cellular senescence and cognition decline in 10 months old mouse hip-pocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc^−/− cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.

Key words： mitochondria; retrograde signal; nucleus; transcription regulation; non-coding RNA; telomerase

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