Mitochondrion-processed <i>TERC</i> regulates senescence without affecting telomerase activities

doi:10.1007/s13238-019-0612-5

Protein Cell

2019, Vol. 10

Issue (9) : 631-648 https://doi.org/10.1007/s13238-019-0612-5

RESEARCH ARTICLE

Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Qian Zheng¹, Peipei Liu¹, Ge Gao¹, Jiapei Yuan¹, Pengfeng Wang², Jinliang Huang¹, Leiming Xie¹, Xinping Lu¹, Fan Di¹, Tanjun Tong^2,³, Jun Chen^2,³, Zhi Lu¹, Jisong Guan¹, Geng Wang¹(

)

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

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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.

Keywords mitochondria retrograde signal nucleus transcription regulation non-coding RNA telomerase

Corresponding Author(s): Geng Wang

Issue Date: 24 September 2019

Cite this article:

Qian Zheng,Peipei Liu,Ge Gao, et al. Mitochondrion-processed TERC regulates senescence without affecting telomerase activities[J]. Protein Cell, 2019, 10(9): 631-648.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-019-0612-5
https://academic.hep.com.cn/pac/EN/Y2019/V10/I9/631

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