Peipei Liu
Ge Gao
Jiapei Yuan
Pengfeng Wang
Jinliang Huang
Leiming Xie
Xinping Lu
Fan Di
Tanjun Tong
Jun Chen
Zhi Lu
Jisong Guan
Geng Wang
1 MOE Key laboratory of Bioinformatics, Cell Biology and Development Center, School of Life Sciences, Tsinghua University, Beijing 100084, China;
2 Peking University Research Center on Aging, Beijing 100191, China;
3 Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China
Funds: This research was supported by the Priority Research Program of the Ministry of Science and Technology of the People's Republic of China 2017YFA0504600, National Natural Science Foundation of the People's Republic of China grant 31371439, 91649103, and Ministry of Education of the People's Republic of China 1000 Talents Youth program.
Received Date: 2018-10-28
Rev Recd Date:2019-01-15
Abstract
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 TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays 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-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi 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.Keywords: mitochondria,
retrograde signal,
nucleus,
transcription regulation,
non-coding RNA,
telomerase
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