RESEARCH ARTICLE

Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

  • Qian Zheng 1 ,
  • Peipei Liu 1 ,
  • Ge Gao 1 ,
  • Jiapei Yuan 1 ,
  • Pengfeng Wang 2 ,
  • Jinliang Huang 1 ,
  • Leiming Xie 1 ,
  • Xinping Lu 1 ,
  • Fan Di 1 ,
  • Tanjun Tong 2,3 ,
  • Jun Chen 2,3 ,
  • Zhi Lu 1 ,
  • Jisong Guan 1 ,
  • Geng Wang , 1
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  • 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

Received date: 28 Oct 2018

Accepted date: 15 Jan 2019

Published date: 15 Sep 2019

Copyright

2019 The Author(s)

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.

Cite this article

Qian Zheng , 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 . Mitochondrion-processed TERC regulates senescence without affecting telomerase activities[J]. Protein & Cell, 2019 , 10(9) : 631 -648 . DOI: 10.1007/s13238-019-0612-5

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