Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Zheng, Qian; Li, Peipei; Gao, Ge; Yuan, Jiapei; Wang, Pengfeng; Huang, Juntong; Xie, Leiming; Lu, Xiaoyong; Di, Fan; Tong, Tanjun; Chen, Jun; Lu, Zhi John; Guan, Ji‐Song; Wang, Geng

doi:10.1007/s13238-019-0612-5

Cited by 42 publications

(42 citation statements)

References 49 publications

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“…It was detected by the RT-PCR in purified mitoplasts, but as as a shorter, 195 nt-long transcript, which was termed TERC-53. Zheng et al (2019) demonstrated that TERC-53 is mostly localized in the cytosol, where it regulates cellular senescence and is involved in cognition decline in mice hippocampus without affecting telomerase activity or mitochondrial functions. Having this in mind, the authors hypothesized that TERC-53 is exported from the mitochondria back to the cytosol (Cheng et al, 2018;Zheng et al, 2019).…”

Section: Housekeeping Ncrnas Localized In Mitochondriamentioning

confidence: 99%

ncRNAs: New Players in Mitochondrial Health and Disease?

Gusic

2020

Front. Genet.

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The regulation of mitochondrial proteome is unique in that its components have origins in both mitochondria and nucleus. With the development of OMICS technologies, emerging evidence indicates an interaction between mitochondria and nucleus based not only on the proteins but also on the non-coding RNAs (ncRNAs). It is now accepted that large parts of the non-coding genome are transcribed into various ncRNA species. Although their characterization has been a hot topic in recent years, the function of the majority remains unknown. Recently, ncRNA species microRNA (miRNA) and long-non coding RNAs (lncRNA) have been gaining attention as direct or indirect modulators of the mitochondrial proteome homeostasis. These ncRNA can impact mitochondria indirectly by affecting transcripts encoding for mitochondrial proteins in the cytoplasm. Furthermore, reports of mitochondria-localized miRNAs, termed mitomiRs, and lncRNAs directly regulating mitochondrial gene expression suggest the import of RNA to mitochondria, but also transcription from the mitochondrial genome. Interestingly, ncRNAs have been also shown to hide small open reading frames (sORFs) encoding for small functional peptides termed micropeptides, with several examples reported with a role in mitochondria. In this review, we provide a literature overview on ncRNAs and micropeptides found to be associated with mitochondrial biology in the context of both health and disease. Although reported, small study overlap and rare replications by other groups make the presence, transport, and role of ncRNA in mitochondria an attractive, but still challenging subject. Finally, we touch the topic of their potential as prognosis markers and therapeutic targets.

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Section: Housekeeping Ncrnas Localized In Mitochondriamentioning

confidence: 99%

ncRNAs: New Players in Mitochondrial Health and Disease?

Gusic

2020

Front. Genet.

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“…Similarly to RMRP, hTERC was found to be processed upon mitochondrial import into a shorter 195 nt-long RNA termed TERC-53. Since the processed version of hTERC was detected mostly in the cytosol, the authors suggested that TERC-53 is re-exported from the mitochondria, which would permit to somehow relay the functional state of the mitochondria to the nucleus and other cellular compartments [25,70]. However, evidence that hTERC processing occurs within the mitochondrial matrix and not at the mitochondrial surface is currently lacking.…”

Section: Mitochondrial Rna Importomementioning

confidence: 99%

Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches

Jeandard

Smirnova

Tarassov

et al. 2019

Cells

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Mitochondria harbor their own genetic system, yet critically depend on the import of a number of nuclear-encoded macromolecules to ensure their expression. In all eukaryotes, selected non-coding RNAs produced from the nuclear genome are partially redirected into the mitochondria, where they participate in gene expression. Therefore, the mitochondrial RNome represents an intricate mixture of the intrinsic transcriptome and the extrinsic RNA importome. In this review, we summarize and critically analyze data on the nuclear-encoded transcripts detected in human mitochondria and outline the proposed molecular mechanisms of their mitochondrial import. Special attention is given to the various experimental approaches used to study the mitochondrial RNome, including some recently developed genome-wide and in situ techniques.

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“…Interestingly, the majority of TERC-53 has been detected in the cytosol instead of mitochondria, and the cytosolic levels of TERC-53 are regulated by mitochondrial functions but have no direct effect on mitochondria (Cheng et al, 2018; Figure 3). The following studies showed that TERC-53 functions as a signaling molecule, relating the functional states of mitochondria to the nucleus, possibly by inhibiting GAPDH nuclear translocalization (Zheng et al, 2019). TERC-53 itself does not affect and is independent of telomerase activity (Zheng et al, 2019).…”

Section: Mitochondrial Localization and Processing Of Tercmentioning

confidence: 99%

“…The following studies showed that TERC-53 functions as a signaling molecule, relating the functional states of mitochondria to the nucleus, possibly by inhibiting GAPDH nuclear translocalization (Zheng et al, 2019). TERC-53 itself does not affect and is independent of telomerase activity (Zheng et al, 2019). The whole process of TERC-53 production and function has been shown to be involved in cellular senescence and organismal aging (Zheng et al, 2019; Figure 3).…”

Section: Mitochondrial Localization and Processing Of Tercmentioning

confidence: 99%

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Mitochondria, Telomeres and Telomerase Subunits

Zheng

Huang

Wang

2019

Front. Cell Dev. Biol.

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Mitochondrial functions and telomere functions have mostly been studied independently. In recent years, it, however, has become clear that there are intimate links between mitochondria, telomeres, and telomerase subunits. Mitochondrial dysfunctions cause telomere attrition, while telomere damage leads to reprogramming of mitochondrial biosynthesis and mitochondrial dysfunctions, which has important implications in aging and diseases. In addition, evidence has accumulated that telomere-independent functions of telomerase also exist and that the protein component of telomerase TERT shuttles between the nucleus and mitochondria under oxidative stress. Our previously published data show that the RNA component of telomerase TERC is also imported into mitochondria, processed, and exported back to the cytosol. These data show a complex regulation network where telomeres, nuclear genome, and mitochondria are co-regulated by multi-localization and multi-function proteins and RNAs. This review summarizes the connections between mitochondria and telomeres, the mitochondrion-related functions of telomerase subunits, and how they play a role in crosstalk between mitochondria and the nucleus.

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Mitochondrion-processed TERC regulates senescence without affecting telomerase activities

Cited by 42 publications

References 49 publications

ncRNAs: New Players in Mitochondrial Health and Disease?

ncRNAs: New Players in Mitochondrial Health and Disease?

Import of Non-Coding RNAs into Human Mitochondria: A Critical Review and Emerging Approaches

Mitochondria, Telomeres and Telomerase Subunits

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