Article

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: 11.98). 03/2013; DOI: 10.1038/cr.2013.37
Source: PubMed

ABSTRACT 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

Full-text

Available from: Wei Yan, Sep 20, 2014
4 Followers
 · 
152 Views
  • Source
    [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.
    Pharmacology [?] Therapeutics 06/2014; DOI:10.1016/j.pharmthera.2014.06.002 · 7.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding gene regulation mechanisms has been a serious challenge in biology. As a novel mechanism, small non-coding RNAs are an alternative means of gene regulation in a specific and efficient manner. There are growing reports on regulatory roles of these RNAs including transcriptional gene silencing/activation and post-transcriptional gene silencing events. Also, there are several known small non-coding RNAs which all work through RNA interference pathway. Interestingly, these small RNAs are secreted from cells toward targeted cells presenting new communication approach in cell-cell or cell-organ signal transduction. In fact, understanding cellular and molecular basis of these pathways will strongly improve developing targeted therapies and potent and specific regulatory tools. This study will review some of the most recent findings in this subject and will introduce a super-pathway RNA interference-based small RNA silencing network.
    Functional & Integrative Genomics 11/2013; 14(1). DOI:10.1007/s10142-013-0344-1 · 2.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Energy metabolism and mitochondrial function hold a core position in cellular homeostasis. Oxidative metabolism is regulated at multiple levels, ranging from gene transcription to allosteric modulation. To accomplish the fine tuning of these multiple regulatory circuits, the nuclear and mitochondrial compartments are tightly and reciprocally controlled. The fact that nuclear encoded factors, PPARγ coactivator 1α and mitochondrial transcription factor A, play pivotal roles in the regulation of oxidative metabolism and mitochondrial biogenesis is paradigmatic of this crosstalk. Here we provide an updated survey of the genetic and epigenetic mechanisms involved in the control of energy metabolism and mitochondrial function. Chromatin dynamics highly depends on post-translational modifications occurring at specific amino acids in histone proteins and other factors associated to nuclear DNA. In addition to the well characterized enzymes responsible for histone methylation/demethylation and acetylation/deacetylation, other factors have gone on the "metabolic stage". This is the case of the new class of α-ketoglutarate-regulated demethylases (Jumonji C domain containing demethylases) and of the NAD+-dependent deacetylases, also known as sirtuins. Moreover, unexpected features of the machineries involved in mitochondrial DNA (mtDNA) replication and transcription, mitochondrial RNA processing and maturation have recently emerged. Mutations or defects of any component of these machineries profoundly affect mitochondrial activity and oxidative metabolism. Finally, recent evidences support the importance of mtDNA packaging in replication and transcription. These observations, along with the discovery that non-classical CpG islands present in mtDNA undergo methylation, indicate that epigenetics also plays a role in the regulation of the mitochondrial genome function.
    Current Genomics 12/2014; 15(6):436-56. DOI:10.2174/138920291506150106151119 · 2.87 Impact Factor