Abstract
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.
Highlights
Molecular biology has historically described RNA as an intermediate between genetic information stored in DNA and protein synthesis
It is becoming apparent that RNAs are not important for cell only in the context of messenger RNAs (mRNAs) as intermediates between DNA and protein, and as powerful players themselves by affecting basically any stage of gene expression
Dozens of non-coding RNAs (ncRNAs) acting in the cytosol have been described to indirectly influence mitochondrial biology, usually by targeting mitochondria-related, nuclear-encoded transcripts
Summary
Molecular biology has historically described RNA as an intermediate between genetic information stored in DNA and protein synthesis. Mitochondria contain their own circular genome (mtDNA) In humans, it is 16,569 bp in length and contains 37 genes- encoding for 2 rRNAs, 22 tRNAs, and 13 proteins of the oxidative phosphorylation (OXPHOS) system (Anderson et al, 1981) (Figure 2). We focus on classes of ncRNAs described to be functionally related with and/or localized in mitochondria: the housekeeping ncRNAs, miRNAs, and lncRNAs. We take up the topic of mitochondrial micropeptides, recently discovered to be encoded within regions initially annotated as non-coding. As about 1,500 nuclear-encoded proteins are imported into mitochondria and involved in diverse mitochondrial functions, many miRNAs have been described as directly targeting their mRNAs in the cytoplasm. SRNA-seq miRNA microarray, immunostaining, RT-qPCR sRNA-seq, RT-qPCR CLIP-seq, miRACE, RTqPCR sRNA-seq, RT-qPCR Microarray, RT-qPCR, CLIPseq, sRNA-seq
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