Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Protein & Cell
Qian ZhengGeng Wang

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.

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Citations

Aug 20, 2020·RNA Biology·Jian Qin, Chantal Autexier
Nov 30, 2019·Frontiers in Cell and Developmental Biology·Qian ZhengGeng Wang
May 5, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Marte MolenaarsRiekelt H Houtkooper
Mar 18, 2020·Frontiers in Genetics·Mirjana Gusic, Holger Prokisch
Apr 12, 2020·Trends in Molecular Medicine·Martina Rossi, Myriam Gorospe
Jun 5, 2019·Bio-protocol·Jinliang Huang, Geng Wang
Jul 29, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Maya Raghunandan, Anabelle Decottignies
Aug 7, 2021·Biomedicines·Simon ToupanceIsabelle Koscinski
Aug 7, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jesús García-CastilloMaría L Cayuela
Aug 21, 2021·Frontiers in Cell and Developmental Biology·Jinliang HuangGeng Wang
Oct 6, 2021·Journal of Extracellular Vesicles·Yujia YinXipeng Wang
Jun 5, 2019··Geng WangJinliang Huang

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Methods Mentioned

BETA
immunoprecipitation
RNAseq
nuclear translocation
Gel shift
PCR
electrophoresis
confocal microscopy

Software Mentioned

GraphPad Prism
R package topGO
TSE multi conditioning system
EthoVision XT
GFOLD
Tophat
TSE conditioning
ImageJ

Related Concepts

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