The mitochondrial genome encodes abundant small noncoding RNAs

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.
Cell Research (Impact Factor: 12.41). 03/2013; 23(6). DOI: 10.1038/cr.2013.37
Source: PubMed


Small noncoding RNAs identified thus far are all encoded by the nuclear genome. Here, we report that the murine and human mitochondrial genomes encode thousands of small noncoding RNAs, which are predominantly derived from the sense transcripts of the mitochondrial genes (host genes), and we termed these small RNAs mitochondrial genome-encoded small RNAs (mitosRNAs). DICER inactivation affected, but did not completely abolish mitosRNA production. MitosRNAs appear to be products of currently unidentified mitochondrial ribonucleases. Overexpression of mitosRNAs enhanced expression levels of their host genes in vitro, and dysregulated mitosRNA expression was generally associated with aberrant mitochondrial gene expression in vivo. Our data demonstrate that in addition to 37 known mitochondrial genes, the mammalian mitochondrial genome also encodes abundant mitosRNAs, which may play an important regulatory role in the control of mitochondrial gene expression in the cell.Cell Research advance online publication 12 March 2013; doi:10.1038/cr.2013.37.

Download full-text


Available from: Loredana Moro, Aug 23, 2015
  • Source
    • "The studies suggested the presence of unique class of small RNAs in the human mitochondria (Mercer et al., 2011; Ro et al., 2013). Apart from this, a subset of the nuclear encoded microRNAs have been shown to localize to the mitochondria (Das et al., 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epigenetic modifications of the nuclear genome have been well studied and it is established that these modifications play a key role in nuclear gene expression. However, the status of mitochondrial epigenetic modifications has not been delved in detail. The recent technological advancements in the genome analyzing tools and techniques, have helped in investigating mitochondrial epigenetic modifications with greater resolution and studies have indicated a regulatory role of the mitochondrial epigenome. Association of mitochondrial DNA methylation with various disease conditions, drug treatment, aging, exposure to environmental pollutants etc. has lent credence to this belief. Herein, we have reviewed studies on mitochondrial epigenetic modifications with a focus to comprehend its regulatory role in gene expression and disease association.
    Full-text · Article · Oct 2015 · Mitochondrion
  • Source
    • "AGO2 was also hypothesized to function as a molecular conveyor for mitochondrial trafficking of miRNAs [59]. In a further work, Ro et al. [76] showed that both the production of mitochondrial small ncRNAs and the expression of mitochondrial genes were strongly affected in Dicer-null mutant mouse cells but they detected neither Dicer nor AGO2 in highly purified mitochondria from human HEK293T cells. As mentioned above, upon analysis of both intact mitochondria and mitoplasts from human HEK293 cells, Sripada et al. [69] in turn proposed that miRNAs, AGO2 and other RNA interference components would actually assemble into RISC complexes associated with target mRNAs bound to the outer membrane at the mitochondrial surface, building a site-specific platform for the regulation of mRNA turnover and translation (Fig. 2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Originally focused on the nuclear and cytosolic compartments, the concept of regulation driven by non-coding RNAs (ncRNAs) is extending to mitochondria and chloroplasts. These organelles have distinct genetic systems that need coordination with cellular demands. In mammals, nuclear-encoded microRNAs were found associated with the mitochondria. Some of these contribute to the regulation of mitochondrial transcription and translation. Others were proposed to be stored in the organelles and to be released for regulation of nuclear transcripts. Further ncRNAs of various sizes derive from the mitochondrial genome and it was speculated that organelles host antisense or RNA interference pathways. Long ncRNAs mapping to the mitochondrial DNA seem to operate in the nucleus. Altogether, the origin and trafficking of ncRNAs categorized as mitochondrial in mammals raise questions far beyond the current knowledge. In protozoa, hundreds of guide RNAs specify editing events needed to generate functional messenger RNAs. Only few ncRNAs have been reported in plant mitochondria, but editing sites were revealed in non-coding regions of the organellar genome, suggesting that the corresponding transcripts have a function. Conversely, numerous ncRNA candidates were identified in chloroplasts, essentially mapping to the plastid genome. A synthetic view of the data with their functional implications is given here. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · Biochimie
  • Source
    • "In addition, some of these drugs increase dopamine levels, which lead to increased formation of ROS. ROS can affect mtDNA copy number and/or damage the mtDNA genome as well as influence chromatin remodeling via ATP level (Maryanovich & Gross, 2013). Furthermore, drugs of abuse influence the epigenetic machinery at several levels, either through the alteration of DNA and histone modifications or through the regulation of DNMTs, miRNAs and transcription factor expression. miRNAs and nuclear-encoded mitochondrial proteins are translocated into the mitochondrion. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Being the centre of energy production in eukaryotic cells, mitochondria are also crucial for various cellular processes including intracellular Ca(2+) signalling and generation of reactive oxygen species (ROS). Mitochondria contain their own circular DNA which encodes not only proteins, transfer RNA and ribosomal RNAs but also non-coding RNAs. The most recent line of evidence indicates the presence of 5-methylcytosine and 5-hydroxymethylcytosine in mitochondrial DNA (mtDNA) thus the level of gene expression - in a way similar to nuclear DNA - can be regulated by direct epigenetic modifications. Up to now, very little data shows the possibility of epigenetic regulation of mtDNA. Mitochondria and mtDNA are particularly important in the nervous system and may participate in the initiation of drug addiction. In fact, some addictive drugs enhance ROS production and generate oxidative stress that in turns alters mitochondrial and nuclear gene expression. This review summarizes recent findings on mitochondrial function, mtDNA copy number and epigenetics in drug addiction.
    Full-text · Article · Jun 2014 · Pharmacology [?] Therapeutics
Show more