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

Jeandard, Damien; Smirnova, Anna; Tarassov, Ivan; Barrey, Éric; Smirnov, Alexandre; Entelis, Nina

doi:10.3390/cells8030286

Cited by 65 publications

(76 citation statements)

References 165 publications

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“…In addition, several groups indicated that mtRNase P is imported into the mitochondrial matrix through interaction with PNPase (Wang et al, 2010;Mercer et al, 2011;Noh et al, 2016) ( Figure 3D). However, as so far functional RNase P ribonucleoprotein has not been reported in mitochondria, the existence of mtRNase P remains controversial (Jeandard et al, 2019).…”

Section: Housekeeping Ncrnas Localized In Mitochondriamentioning

confidence: 99%

“…also reported the presence of ncRNAs encoded by the nuclear DNA, especially miRNAs and lncRNAs, within mitochondria across various cell types and tissues, suggesting that these ncRNAs may play important roles in the mitochondrial homeostasis (Kim et al, 2017b;Jeandard et al, 2019). The summary of the proposed nuclear-encoded ncRNAs is given in Table 1.…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

ncRNAs: New Players in Mitochondrial Health and Disease?

Gusic

2020

Front. Genet.

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“…While the import of small non-coding RNAs has been observed throughout eukaryotes, the process is not nearly as well-understood as the mitochondrial protein import pathway, nor does it appear to be as efficient. 40 However, there have been promising preliminary results in this area, including the discovery of a 20-bp RNA sequence that appears to facilitate the import of both non-coding RNAs as well as mRNAs. 41 Unfortunately, for these mtDNA-encoded proteins, even forcing the import of an allotopically-expressed version of the protein may not be as simple of a solution as it initially appears.…”

Section: Special Considerations Based On Mitochondrial Biologymentioning

confidence: 99%

The special considerations of gene therapy for mitochondrial diseases

Slone

Huang

2020

npj Genom. Med.

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The recent success of gene therapy across multiple clinical trials has inspired a great deal of hope regarding the treatment of previously intractable genetic diseases. This optimism has been extended to the prospect of gene therapy for mitochondrial disorders, which are not only particularly severe but also difficult to treat. However, this hope must be tempered by the reality of the mitochondrial organelle, which possesses specific biological properties that complicate genetic manipulation. In this perspective, we will discuss some of these complicating factors, including the unique pathways used to express and import mitochondrial proteins. We will also present some ways in which these challenges can be overcome by genetic manipulation strategies tailored specifically for mitochondrial diseases.

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“…Selected nucleus-derived ncRNAs are possibly imported into the mitochondria, where they can be involved in multiple mitochondrial biological processes to act as "messengers" between the nucleus and the mitochondria (Vendramin et al, 2017;Jeandard et al, 2019). All the microRNAs present in mitochondria are also called mitomiRNAs (mitomiRs), which is commonly used in some reports (Rippo et al, 2014;Duarte et al, 2015;Giuliani et al, 2018).…”

Section: Nucleus-derived Non-coding Rnas That Target Mtdna Encoded Genesmentioning

confidence: 99%

Mitoepigenetics and Its Emerging Roles in Cancer

Dong

Cui

2020

Front. Cell Dev. Biol.

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In human beings, there is a ∼16,569 bp circular mitochondrial DNA (mtDNA) encoding 22 tRNAs, 12S and 16S rRNAs, 13 polypeptides that constitute the central core of ETC/OxPhos complexes, and some non-coding RNAs. Recently, mtDNA has been shown to have some covalent modifications such as methylation or hydroxylmethylation, which play pivotal epigenetic roles in mtDNA replication and transcription. Posttranslational modifications of proteins in mitochondrial nucleoids such as mitochondrial transcription factor A (TFAM) also emerge as essential epigenetic modulations in mtDNA replication and transcription. Post-transcriptional modifications of mitochondrial RNAs (mtRNAs) including mt-rRNAs, mt-tRNAs and mt-mRNAs are important epigenetic modulations. Besides, mtDNA or nuclear DNA (n-DNA)-derived non-coding RNAs also play important roles in the regulation of translation and function of mitochondrial genes. These evidences introduce a novel concept of mitoepigenetics that refers to the study of modulations in the mitochondria that alter heritable phenotype in mitochondria itself without changing the mtDNA sequence. Since mitochondrial dysfunction contributes to carcinogenesis and tumor development, mitoepigenetics is also essential for cancer. Understanding the mode of actions of mitoepigenetics in cancers may shade light on the clinical diagnosis and prevention of these diseases. In this review, we summarize the present study about modifications in mtDNA, mtRNA and nucleoids and modulations of mtDNA/nDNA-derived non-coding RNAs that affect mtDNA translation/function, and overview recent studies of mitoepigenetic alterations in cancer.

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

Cited by 65 publications

References 165 publications

ncRNAs: New Players in Mitochondrial Health and Disease?

ncRNAs: New Players in Mitochondrial Health and Disease?

The special considerations of gene therapy for mitochondrial diseases

Mitoepigenetics and Its Emerging Roles in Cancer

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