Advertisement

Topics

The MELAS mutation m.3243A>G alters the expression of mitochondrial tRNA fragments.

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "The MELAS mutation m.3243A>G alters the expression of mitochondrial tRNA fragments."

Recent evidences highlight the importance of mitochondria-nucleus communication for the clinical phenotype of oxidative phosphorylation (OXPHOS) diseases. However, the participation of small non-coding RNAs (sncRNAs) in this communication has been poorly explored. We asked whether OXPHOS dysfunction alters the production of a new class of sncRNAs, mitochondrial tRNA fragments (mt tRFs), and, if so, whether mt tRFs play a physiological role and their accumulation is controlled by the action of mt tRNA modification enzymes. To address these questions, we used a cybrid model of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), an OXPHOS disease mostly caused by mutation m.3243A>G in the mitochondrial tRNA gene. High-throughput analysis of small-RNA-Seq data indicated that m.3243A>G significantly changed the expression pattern of mt tRFs. A functional analysis of potential mt tRFs targets (performed under the assumption that these tRFs act as miRNAs) indicated an association with processes that involve the most common affected tissues in MELAS. We present evidences that mt tRFs may be biologically relevant, as one of them (mt i-tRF GluUUC), likely produced by the action of the nuclease Dicer and whose levels are Ago2 dependent, down-regulates the expression of mitochondrial pyruvate carrier 1 (MPC1), promoting the build-up of extracellular lactate. Therefore, our study underpins the idea that retrograde signaling from mitochondria is also mediated by mt tRFs. Finally, we show that accumulation of mt i-tRF GluUUC depends on the modification status of mt tRNAs, which is regulated by the action of stress-responsive miRNAs on mt tRNA modification enzymes.

Affiliation

Journal Details

This article was published in the following journal.

Name: Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Pages:

Links

DeepDyve research library

PubMed Articles [15932 Associated PubMed Articles listed on BioPortfolio]

The Usefulness of Muscle Biopsy in Initial Diagnostic Evaluation of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes.

The disease entity mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by an early onset of stroke-like episodes. MELAS is the most dominant subtype of ...

Mitochondrial A3243G mutation causes mitochondrial encephalomyopathy in a Chinese patient: Case report.

Mitochondrial mutations are associated with a wide spectrum of clinical abnormalities. More than half of these mutations are distributed in the 22 mitochondrial tRNA genes, including tRNA. In particul...

Elevation in plasma tRNA fragments precede seizures in human epilepsy.

Transfer RNAs (tRNAs) are a major class of noncoding RNA. Stress-induced cleavage of tRNA is highly conserved and results in tRNA fragments. Here we find specific tRNA fragments in plasma are associat...

A novel variant m.641A>T in the mitochondrial MT-TF gene is associated with epileptic encephalopathy in adolescent.

We present a 14-year-old girl with loss of motor functions, tetraplegia, epilepsy and nystagmus, caused by a novel heteroplasmic m.641A>T transition in an evolutionary conserved region of mitochondria...

MELAS and macroangiopathy: A case report and literature review.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are thought to be rarely accompanied by macroangiopathy. We reported a case of MELAS that presented right distal internal...

Clinical Trials [3364 Associated Clinical Trials listed on BioPortfolio]

DINAMITE Study Nutritional State and Effect Diet in Mitochondrial Disease

The m.3243A>G mutation is the most frequent cause of mitochondrial disease in adults, for which currently no therapy is available and treatment is solely supportive. Since both malnutritio...

L-Citrulline Dose Finding Safety Study in MELAS

The main purpose of this study is to determine the safest maximum dose of an amino acid, citrulline, which will be used as potential treatment for adult patients with a disorder of energy ...

A Dose-escalating Clinical Trial With KH176

Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for ...

Evaluating the Effectiveness of a Dichloroacetate in MELAS Syndrome

Patients with the MELAS syndrome experience devastating mental impairment. This study will evaluate the effectiveness of the drug dichloroacetate (DCA) to reduce the symptoms of MELAS.

The KHENERGY Study

Mitochondrial Diseases are rare, progressive, multi-system, often-early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for...

Medical and Biotech [MESH] Definitions

A dioxygenase and alkylation repair homolog that catalyzes the methylation of 5-carboxymethyl URIDINE to 5-methylcarboxymethyl uridine at the wobble position of the ANTICODON loop in TRANSFER RNA (tRNA) via its methyltransferase domain. It has a preference for tRNA (ARGININE) and tRNA (GLUTAMATE), and does not bind tRNA (LYSINE).

A modified nucleoside which is present in the first position of the anticodon of tRNA-tyrosine, tRNA-histidine, tRNA-asparagine and tRNA-aspartic acid of many organisms. It is believed to play a role in the regulatory function of tRNA. Nucleoside Q can be further modified to nucleoside Q*, which has a mannose or galactose moiety linked to position 4 of its cyclopentenediol moiety.

A mutation that results in an increase in a gene's activity or in acquiring a new molecular function or a new pattern of gene expression.

A mitochondrial uncoupling protein that is expressed in many tissues and exhibits the greatest expression in SKELETAL MUSCLE. It regulates mitochondrial ATP production and the generation of REACTIVE OXYGEN SPECIES.

A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Mental Health
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...


Searches Linking to this Article