Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation

Bravo, Juan I.; Nozownik, Séverine; Danthi, Prakroothi S; Benayoun, Bérénice A.

doi:10.1242/dev.175786

Cited by 28 publications

(29 citation statements)

References 261 publications

(311 reference statements)

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“…These pathways, which represent both adaptive and maladaptive cellular responses, refer to a series of genes related to glycolysis for energy production, antioxidant and redox regulatory systems, autophagy/mitophagy, apoptosis, chromatin remodelling, and compartment-specific unfolded protein stress response. In this context, nuclear mRNAs or non-coding RNAs of either nuclear or mitochondrial origin, such as processed mt-tRNA fragments exported to the cytoplasm or circular RNAs [ 40 , 42 , 43 , 44 ], may represent possible targets of cytosolic RNA-binding proteins for regulation of nuclear gene expression. In addition to mitochondrial retrograde signalling to the cytoplasm, the full recovery of cell viability might be the result of Cterm capacity to bind cytosolic RNA targets.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype

Capriglia

Rizzo

Petrosillo

et al. 2021

Life

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The m.3243A>G mutation within the mitochondrial mt-tRNALeu(UUR) gene is the most prevalent variant linked to mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome. This pathogenic mutation causes severe impairment of mitochondrial protein synthesis due to alterations of the mutated tRNA, such as reduced aminoacylation and a lack of post-transcriptional modification. In transmitochondrial cybrids, overexpression of human mitochondrial leucyl-tRNA synthetase (LARS2) has proven effective in rescuing the phenotype associated with m.3243A>G substitution. The rescuing activity resides in the carboxy-terminal domain (Cterm) of the enzyme; however, the precise molecular mechanisms underlying this process have not been fully elucidated. To deepen our knowledge on the rescuing mechanisms, we demonstrated the interactions of the Cterm with mutated mt-tRNALeu(UUR) and its precursor in MELAS cybrids. Further, the effect of Cterm expression on mitochondrial functions was evaluated. We found that Cterm ameliorates de novo mitochondrial protein synthesis, whilst it has no effect on mt-tRNALeu(UUR) steady-state levels and aminoacylation. Despite the complete recovery of cell viability and the increase in mitochondrial translation, Cterm-overexpressing cybrids were not able to recover bioenergetic competence. These data suggest that, in our MELAS cell model, the beneficial effect of Cterm may be mediated by factors that are independent of the mitochondrial bioenergetics.

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Section: Discussionmentioning

confidence: 99%

Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype

Capriglia

Rizzo

Petrosillo

et al. 2021

Life

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“…Additionally, other non-coding RNAs appear to act as epigenetic regulators. For instance, there is a growing body of evidence suggesting that small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), circular RNAs (circRNAs), piwi-interacting RNAs (piRNAs), or long non-coding (lncRNAs) have a pivotal role in the epigenetic landscape (reviewed elsewhere [ 100 , 101 , 102 ]). However, the direct relationship between these non-coding RNAs and nutrition still remains unknown.…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review

Marín-Garcia

Llobat

2021

Animals

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Epigenetic changes regulate gene expression and depend of external factors, such as environment and nutrition. In pigs, several studies on protein nutrition have been performed to improve productive and reproductive traits. Indeed, these studies aimed not only to determine broad protein requirements but also pigs’ essential amino acids requirements. Moreover, recent studies tried to determine these nutritional requirements for each individual, which is known as protein precision nutrition. However, nutritional changes could affect different epigenetic mechanisms, modifying metabolic pathways both in a given individual and its offspring. Modifications in protein nutrition, such as change in the amino acid profile, increase or decrease in protein levels, or the addition of metabolites that condition protein requirements, could affect the regulation of some genes, such as myostatin, insulin growth factor, or genes controlling cholesterol and glucose metabolism pathways. This review summarizes the impact of most common protein nutritional strategies on epigenetic changes and describes their effects on regulation of gene expression in pigs. In a context where animal nutrition is shifting towards precision protein nutrition (PPN), further studies evaluating the effects of PPN on animal epigenetic are necessary.

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“…Furthermore, TE recombination events are associated with early-onset PD. Bravo et al, (2018) reported five structural variations in the PRKN gene, which is the most frequently mutated gene in this condition, including deletions and exon rearrangements, all of which were caused by recombinatory events triggered by TE reactivation [ 83 ]. It was also reported that pathogenic Tau protein leads to a decrease in piRNA-mediated regulation, which increases TE retrotransposition in PD neurons, triggering oxidative stress and cell death [ 84 , 85 ].…”

Section: Genetic Alterations In Parkinson’s Diseasementioning

confidence: 99%

Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson’s Disease

Cabral

Schaan

Cavalcante

et al. 2021

IJMS

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Background: Parkinson’s disease (PD) is currently the second most common neurodegenerative disorder, burdening about 10 million elderly individuals worldwide. The multifactorial nature of PD poses a difficult obstacle for understanding the mechanisms involved in its onset and progression. Currently, diagnosis depends on the appearance of clinical signs, some of which are shared among various neurologic disorders, hindering early diagnosis. There are no effective tools to prevent PD onset, detect the disease in early stages or accurately report the risk of disease progression. Hence, there is an increasing demand for biomarkers that may identify disease onset and progression, as treatment-based medicine may not be the best approach for PD. Over the last few decades, the search for molecular markers to predict susceptibility, aid in accurate diagnosis and evaluate the progress of PD have intensified, but strategies aimed to improve individualized patient care have not yet been established. Conclusions: Genomic variation, regulation by epigenomic mechanisms, as well as the influence of the host gut microbiome seem to have a crucial role in the onset and progress of PD, thus are considered potential biomarkers. As such, the human nuclear and mitochondrial genome, epigenome, and the host gut microbiome might be the key elements to the rise of personalized medicine for PD patients.

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Transposable elements, circular RNAs and mitochondrial transcription in age-related genomic regulation

Cited by 28 publications

References 261 publications

Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype

Exploring the Ability of LARS2 Carboxy-Terminal Domain in Rescuing the MELAS Phenotype

How Does Protein Nutrition Affect the Epigenetic Changes in Pig? A Review

Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson’s Disease

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