Mitochondrial Trafficking and Processing of Telomerase RNA TERC

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

doi:10.1016/j.celrep.2018.08.003

Cited by 64 publications

(68 citation statements)

References 30 publications

(47 reference statements)

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“…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). However, this hypothesis indicates hTERC processing occurring within the mitochondria, which has so far not been reported.…”

Section: Housekeeping Ncrnas Localized In Mitochondriamentioning

confidence: 99%

“…hTERC is the RNA component of the human telomerase, where it serves as a sequence template for the telomere replication (Gall, 1990). As its sequence contains a region similar to an RMRP and RNase P short stem-loop that was proposed to enable their entry into mitochondria (Wang et al, 2010), hTERC was also proposed to be mitochondria-localized (Cheng et al, 2018). It was detected by the RT-PCR in purified mitoplasts, but as as a shorter, 195 nt-long transcript, which was termed TERC-53.…”

Section: Housekeeping Ncrnas Localized In Mitochondriamentioning

confidence: 99%

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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%

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 catalytic subunit of telomerase, TERT, can be localized in the mitochondria where it plays a protective role for metabolism and DNA maintenance (Ahmed et al, ). Telomerase RNA can be processed within the mitochondria (Cheng et al, ), and some shelterin subunits have been shown to have mitochondrial functions (Chen et al, ; Kim et al, ). Telomere dysfunction activates p53, which in turn binds and represses PGC1‐ α and PGC1‐ β promoters leading to mitochondrial dysfunction (Chang et al, ; Sahin et al, ).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

et al. 2020

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Telomere shortening follows a developmentally regulated process that leads to replicative senescence of dividing cells. However, whether telomere changes are involved in postmitotic cell function and aging remains elusive. In this study, we discovered that the level of the TRF2 protein, a key telomere‐capping protein, declines in human skeletal muscle over lifetime. In cultured human myotubes, TRF2 downregulation did not trigger telomere dysfunction, but suppressed expression of the mitochondrial Sirtuin 3 gene (SIRT3) leading to mitochondrial respiration dysfunction and increased levels of reactive oxygen species. Importantly, restoring the Sirt3 level in TRF2‐compromised myotubes fully rescued mitochondrial functions. Finally, targeted ablation of the Terf2 gene in mouse skeletal muscle leads to mitochondrial dysfunction and sirt3 downregulation similarly to those of TRF2‐compromised human myotubes. Altogether, these results reveal a TRF2‐SIRT3 axis controlling muscle mitochondrial function. We propose that this axis connects developmentally regulated telomere changes to muscle redox metabolism.

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“…We provide indications that mecciRNAs may shuttle in and out of the mitochondria, but how they are exported and imported remains elusive. mecciRNAs interact with PNPASE, an enzyme has been demonstrated to be essential for mitochondrial importation of RMRP and several other noncoding RNAs (Cheng et al, 2018;Wang et al, 2010). Recently, it is shown that dsRNAs derived from mitochondria play PNPASE related roles (Dhir et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Some nuclear-encoded noncoding RNAs such as MRP RNA (RMRP), 5S rRNA, and certain tRNAs are also imported into mitochondria, although the mitochondrial RNA importation mechanism is much less understood (Smirnov et al, 2010;Wang et al, 2010) . It has been known that a polynucleotide phosphorylase (PNPASE) PNPT1 residing in the intermembrane space plays an unanticipated role in mitochondrial RNA importation (Cheng et al, 2018;Wang et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

The identification of mecciRNAs and their roles in mitochondrial entry of proteins

Liu

Wang

et al. 2019

Preprint

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Mammalian mitochondria have small genomes encoding very limited numbers of proteins. Over one thousand proteins and noncoding RNAs encoded by nuclear genome have to be imported from the cytosol into the mitochondria. Here we report the identification of hundreds of circular RNAs (mecciRNAs) encoded by mitochondrial genome. We provide both in vitro and in vivo evidence to show that mecciRNAs facilitate mitochondrial entry of nuclear-encoded proteins by serving as molecular chaperones in the folding of imported proteins. Known components of mitochondrial protein and RNA importation such as TOM40 and PNPASE interact with mecciRNAs and regulate protein entry. Expression of mecciRNAs is regulated, and these transcripts are critical for mitochondria in adapting to physiological conditions and diseases such as stresses and cancers by modulating mitochondrial protein importation. mecciRNAs and their associated physiological roles add categories and functions to eukaryotic circular RNAs, and shed novel lights on communication between mitochondria and nucleus.

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Mitochondrial Trafficking and Processing of Telomerase RNA TERC

Cited by 64 publications

References 30 publications

ncRNAs: New Players in Mitochondrial Health and Disease?

ncRNAs: New Players in Mitochondrial Health and Disease?

Mitochondrial function in skeletal myofibers is controlled by a TRF2‐SIRT3 axis over lifetime

The identification of mecciRNAs and their roles in mitochondrial entry of proteins

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