scholarly journals A new member in the Argonaute crew: the mt-miRNAs

2020 ◽  
Author(s):  
Andrea Pozzi ◽  
Damian K. Dowling
Keyword(s):  
Gene Regulation ◽  
Rna Interference ◽  
Mitochondrial Genome ◽  
Life Histories ◽  
Energy Production ◽  
Nuclear Gene ◽  
Context Dependency ◽  
Present Evidence ◽  
Nuclear Gene Regulation ◽  
Genotypic Effects

SummaryMutations within the mitochondrial genome have been linked to many diverse phenotypes. Moreover, the effects of these mutations have been shown to differ across sexes and environments. The mechanisms that explain the manifold array of mitochondrial genotypic effects on organismal function, and their context-dependency, have however remained a mystery. Here, we present evidence that mitochondria are involved in nuclear gene regulation via RNA interference; transcribing mitochondrial (mt-)miRNAs that may repress the transcription of nuclear genes that previously had no known involvement in mitochondrial function. Our findings uncover a new mechanism by which mitochondria may shape the expression of animal life-histories and health components; implying that the influence of the mitochondria in regulating organismal function extends well beyond the process of energy production.

scholarly journals Clues of in vivo nuclear gene regulation by mitochondrial short non-coding RNAs

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marco Passamonti ◽  
Marco Calderone ◽  
Manuel Delpero ◽  
Federico Plazzi
Keyword(s):  
Gene Regulation ◽  
Nuclear Gene ◽  
Non Coding Rnas ◽  
Nuclear Gene Regulation

scholarly journals Regulation and imaging of gene expression via an RNA interference antagonistic biomimetic probe

2017 ◽  
Vol 8 (7) ◽  
pp. 4973-4977 ◽  
Author(s):  
Kai Zhang ◽  
Xue-Jiao Yang ◽  
Wei Zhao ◽  
Ming-Chen Xu ◽  
Jing-Juan Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Rna Interference ◽  
Living Cells

A versatile strategy is reported which permits gene regulation and imaging in living cells via an RNA interference antagonistic probe.

Pursuing gene regulation 'logic' via RNA interference and chromatin immunoprecipitation

2006 ◽  
Vol 7 (7) ◽  
pp. 692-697 ◽  
Author(s):  
Caiyi C Li ◽  
Vladimir R Ramirez-Carrozzi ◽  
Stephen T Smale
Keyword(s):  
Gene Regulation ◽  
Rna Interference ◽  
Chromatin Immunoprecipitation

scholarly journals Nuclear pseudogenes of mtDNA (NUMTS) suggest repeated distant inter-species hybridization among direct human ancestors

2017 ◽  
Author(s):  
Konstantin Gunbin ◽  
Konstantin Popadin ◽  
Leonid Peshkin ◽  
Sofia Annis ◽  
Zoe Fleischmann ◽  
...  
Keyword(s):  
Mitochondrial Genome ◽  
Population Size ◽  
Genetic Exchange ◽  
Ancestral Population ◽  
Functional Genes ◽  
Human Lineage ◽  
Present Evidence ◽  
Znf230 Gene ◽  
Species Hybridization ◽  
Human Chromosome 5

Introduction: Increasingly, the emergence and evolution of our species is being tied to genetic exchange between divergent lineages within ~1Ma (e.g., Neanderthals, Denisovans). However, little is known about genetic exchange during earlier (pre-1Ma) human evolution and between more divergent lineages. Results: We present evidence of hybridization within human lineage, show that it likely happened between highly divergent (~4.5My) lineages, more than once. We use analysis of nuclear pseudogenes of mtDNA (“NUMTs”). NUMTs are considered “mtDNA fossils”, as they preserve sequences of ancient mtDNA because mutational rate in the nucleus is much lower than in mtDNA. We demonstrate that a NUMT on human chromosome 5, which is shared by chimpanzee and gorilla, had descended from a mitochondrial genome that had been divergent from our ancestor’s mtDNA by ~4.5% at the time of pseudogene insertion. This implies that this pseudogene should have been inserted in a hominid that at that time had been diverged by about 4.5My of evolution from the hominid that at that time carried our mtDNA lineage. In order for this pseudogene and our mtDNA to end up in the same body, these two hominids should have mated with each other. The large divergence implies a distant interspecies (or even inter-generic) hybridization. Additionally, analysis of two other NUMTs (on Chr11 and Chr7) suggests that hybridization events occurred repeatedly. To exclude the large ancestral population size effect we show that mtDNA divergence in extant ape populations does not depend on population size. Discussion: It is thought that within mammals, it takes ~2-4My to establish reproductive isolation. However, fertile inter-generic hybrids have been documented among several primates, separated by ca. 4My. Very recently, hybridization between Colobine genera separated by ~5 My was reported to involve a NUMT scenario similar to what we had proposed human ancestors. Interestingly, phylogenic analysis consistently places the chr5 NUMT insertion around the time of the Homo/Pan split. Intriguingly, certain hominin fossils of that epoch have been interpreted alternately as more human-like or more ape-like. Such morphological mosaicisity could potentially be explained by hybridization. Fixation of NUMTs in question within population should have been rather efficient, since these pseudogenes appear to have been fixed in more than one population. Thus their spread across populations might have been driven by selection. Indeed, NUMTs on chr5 and chr11 are located in 3’ regions of functional genes. Most intriguingly, Ps11 is located 3’ to the RNF141/ZNF230 gene, essential for spermatogenesis. NUMT might have served as an expression modifier for RNF141, resulting in reproductive advantage. Indeed, RNF141 demonstrates selectively driven expression shift in testis of the ancestor of hominines.

Abstract 276: Angiotensin AT1 Receptor Blockade Reverses Age-Related Changes in Myocardial Energy Metabolism and Increases Mitochondrial Biogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Peter M Abadir ◽  
Ashwin Akki ◽  
Robert Carey ◽  
Ashish Gupta ◽  
Vadappuram Chacko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Metabolism ◽  
Mitochondrial Biogenesis ◽  
Energy Production ◽  
Nuclear Gene ◽  
At1 Receptor ◽  
Resonance Spectroscopy ◽  
Receptor Blockade ◽  
Lv Mass ◽  
Old Mice

Aging and mitochondrial function have been closely linked. We recently reported the identification of a mitochondrial angiotensin system. We hypothesized that angiotensin AT1 receptor blockade would increase energy production and mitochondrial biogenesis and reduce oxidative stress in aging hearts. We used Magnetic resonance spectroscopy to measure cardiac energy metabolism and function in young (20 wks old), aged (150 wks old) mice at baseline and after 4 weeks of losartan (50 mg/kg/day). For mitobiogenesis, qPCR was used to calculate CytB (mitochondrial gene)/GAPDH (nuclear gene) ratio and to measure mito-survival genes Sirt1, Sirt3, Nampt, and PGC-1α. Cardiomyocyte mitochondria from young, aged and treated mice were examined with electron microscopy. The expression of nitrotyrosine was quantified by immunohistochemistry. Older animals hearts (n=9) exhibited increase in LV mass (103±9 mg versus 120±8 mg, young (n=8) versus old (n=9), P<0.002). The mean cardiac PCr/ATP was reduced in older animals (1.5±0.2) than that of young mice (2.0±0.3, P<0.0004). Losartan abolished the LV mass increase in older animals (109±11 mg vs 101±7 mg, young versus old, P<0.1) and improved the impaired energy metabolism of the older hearts increasing the PCr/ATP ratios towards those observed in younger animals (1.94±0.01 vs 1.87±0.4, control versus old, P<0.7). Losartan increased EF in older animals (56±5% vs 63±5%, old versus old treated, P<0.01). Losartan increased mitobiogenesis in the hearts of treated young and old mice (3.8+2.5 folds, P<0.02 and 4.3+ 0.9 folds, P<0.0001). Mito-survival genes in the heart were not increased but PGC-1α was up-regulated by 2.8+1.6-fold, P<0.05 and 7+ 1.9-fold, P<0.001 in young and old treated mice. Electron micrograph analysis revealed that aging was associated with swollen cardiac mitochondria and disrupted cristae, which were reversed by Losartan. Losartan in older animals significantly reduced oxidative damage as evidenced by less Nitrotyrosine staining score in cardiomyocytes (2.5±0.5 vs. 1.3±0.4, old versus old treated, P<0.0009). Our results indicate that Losartan in aging increased mitobiogenesis, reduced oxidative stress, improved energy production and restored cardiac function to the healthy young adult level.

scholarly journals Thyroid hormone action in mitochondria

2001 ◽  
Vol 26 (1) ◽  
pp. 67-77 ◽  
Author(s):  
C Wrutniak-Cabello ◽  
F Casas ◽  
G Cabello
Keyword(s):  
Transcription Factor ◽  
Protein Synthesis ◽  
Thyroid Hormone ◽  
Mitochondrial Genome ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Nuclear Gene ◽  
Short Term ◽  
Inner Membrane ◽  
Stimulation Of

Triiodothyronine (T3) is considered a major regulator of mitochondrial activity. In this review, we show evidence of the existence of a direct T3 mitochondrial pathway, and try to clarify the respective importance of the nuclear and mitochondrial pathways for organelle activity. Numerous studies have reported short-term and delayed T3 stimulation of mitochondrial oxygen consumption. Convincing data indicate that an early influence occurs through an extra-nuclear mechanism insensitive to inhibitors of protein synthesis. Although it has been shown that diiodothyronines could actually be T3 mediators of this short-term influence, the detection of specific T3-binding sites, probably corresponding to a 28 kDa c-Erb Aalpha1 protein of the inner membrane, also supports a direct T3 influence. The more delayed influence of thyroid hormone upon mitochondrial respiration probably results from mechanisms elicited at the nuclear level, including changes in phospholipid turnover and stimulation of uncoupling protein expression, leading to an increased inner membrane proton leak. However, the involvement of a direct mitochondrial T3 pathway leading to a rapid stimulation of mitochondrial protein synthesis has to be considered. Both pathways are obviously involved in the T3 stimulation of mitochondrial genome transcription. First, a 43 kDa c-Erb Aalpha1 protein located in the mitochondrial matrix (p43), acting as a potent T3-dependent transcription factor of the mitochondrial genome, induces early stimulation of organelle transcription. In addition, T3 increases mitochondrial TFA expression, a mitochondrial transcription factor encoded by a nuclear gene. Similarly, the stimulation of mitochondriogenesis by thyroid hormone probably involves both pathways. In particular, the c-erb Aalpha gene simultaneously encodes a nuclear and a mitochondrial T3 receptor (p43), thus ensuring coordination of the expression of the mitochondrial genome and of nuclear genes encoding mitochondrial proteins. Recent studies concerning the physiological importance of the direct mitochondrial T3 pathway involving p43 led to the conclusion that it is not only involved in the regulation of fuel metabolism, but also in the regulation of cell differentiation. As the processes leading to or resulting from differentiation are energy-consuming, p43 coordination of metabolism and differentiation could be of significant importance in the regulation of development.

scholarly journals Ash2 acts as an ecdysone receptor coactivator by stabilizing the histone methyltransferase Trr

2013 ◽  
Vol 24 (3) ◽  
pp. 361-372 ◽  
Author(s):  
Albert Carbonell ◽  
Alexander Mazo ◽  
Florenci Serras ◽  
Montserrat Corominas
Keyword(s):  
Gene Regulation ◽  
Histone Modifications ◽  
Transcriptional Activation ◽  
Histone H3 ◽  
Histone Methyltransferase ◽  
Ecdysone Receptor ◽  
Related Protein ◽  
Molting Hormone ◽  
Set Domain ◽  
Present Evidence

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain–containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is required for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator.

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