Small mitochondrial RNAs as mediators of nuclear gene regulation, and potential implications for human health

BioEssays ◽  
2021 ◽  
pp. 2000265
Author(s):  
Andrea Pozzi ◽  
Damian K. Dowling
Keyword(s):  
Gene Regulation ◽  
Human Health ◽  
Nuclear Gene ◽  
Nuclear Gene Regulation

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 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 Balanced mitochondrial and cytosolic translatomes underlie the biogenesis of human respiratory complexes

2021 ◽  
Author(s):  
Iliana C Soto ◽  
Mary Couvillion ◽  
Erik McShane ◽  
Katja G Hansen ◽  
J. Conor Moran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Mitochondrial Dna ◽  
Nuclear Gene ◽  
Cell Types ◽  
Ribosome Profiling ◽  
Nuclear Gene Expression ◽  
Leigh’S Syndrome ◽  
Cellular Compartments ◽  
Translation Systems

Oxidative phosphorylation (OXPHOS) complexes consist of nuclear and mitochondrial DNA- encoded subunits. Their biogenesis requires cross-compartment gene regulation to mitigate the accumulation of disproportionate subunits. To determine how human cells coordinate mitochondrial and nuclear gene expression processes, we established an optimized ribosome profiling approach tailored for the unique features of the human mitoribosome. Analysis of ribosome footprints in five cell types revealed that average mitochondrial synthesis rates corresponded precisely to cytosolic rates across OXPHOS complexes. Balanced mitochondrial and cytosolic synthesis did not rely on rapid feedback between the two translation systems. Rather, LRPPRC, a gene associated with Leigh's syndrome, is required for the reciprocal translatomes and maintains cellular proteostasis. Based on our findings, we propose that human mitonuclear balance is enabled by matching OXPHOS subunit synthesis rates across cellular compartments, which may represent a vulnerability for cellular proteostasis.

scholarly journals A crystallographic study of human NONO (p54nrb): overcoming pathological problems with purification, data collection and noncrystallographic symmetry

2016 ◽  
Vol 72 (6) ◽  
pp. 761-769 ◽  
Author(s):  
Gavin J. Knott ◽  
Santosh Panjikar ◽  
Andrea Thorn ◽  
Archa H. Fox ◽  
Maria R. Conte ◽  
...  
Keyword(s):  
Data Collection ◽  
Nuclear Gene ◽  
Beam Width ◽  
Molecular Replacement ◽  
X Rays ◽  
Space Group ◽  
Pou Domain ◽  
Structure Solution ◽  
Oriented Parallel ◽  
Nuclear Gene Regulation

Non-POU domain-containing octamer-binding protein (NONO, a.k.a. p54nrb) is a central player in nuclear gene regulation with rapidly emerging medical significance. NONO is a member of the highly conservedDrosophilabehaviour/human splicing (DBHS) protein family, a dynamic family of obligatory dimeric nuclear regulatory mediators. However, work with the NONO homodimer has been limited by rapid irreversible sample aggregation. Here, it is reported that L-proline stabilizes purified NONO homodimers, enabling good-quality solution small-angle X-ray structure determination and crystallization. NONO crystallized in the apparent space groupP21with a unique axis (b) of 408.9 Å and with evidence of twinning, as indicated by the cumulative intensity distributionLstatistic, suggesting the possibility of space groupP1. Structure solution by molecular replacement shows a superhelical arrangement of six NONO homodimers (or 12 inP1) oriented parallel to the long axis, resulting in extensive noncrystallographic symmetry. Further analysis revealed that the crystal was not twinned, but the collected data suffered from highly overlapping reflections that obscured theL-test. Optimized data collection on a new crystal using higher energy X-rays, a smaller beam width and an increased sample-to-detector distance produced non-overlapping reflections to 2.6 Å resolution. The steps taken to analyse and overcome this series of practical difficulties and to produce a biologically informative structure are discussed.

Lycopene alleviates sulfamethoxazole-induced hepatotoxicity in grass carp (Ctenopharyngodon idellus) via suppression of oxidative stress, inflammation and apoptosis

2020 ◽  
Vol 11 (10) ◽  
pp. 8547-8559
Author(s):  
Hongjing Zhao ◽  
Yu Wang ◽  
Mengyao Mu ◽  
Menghao Guo ◽  
Hongxian Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Secondary Metabolites ◽  
Human Health ◽  
Grass Carp ◽  
Aquatic Environment ◽  
Ctenopharyngodon Idellus

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.

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