Search Results (5)

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020, we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients, their families and mouse models (Cc2d1a +/− and valproic acid treated males). Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/−) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels vary by changes in RNA/DNA structure during development, thereby creating transcription alteration and cell memory. Behavioral tests were conducted on the offspring of Cc2d1a (+/−) mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells via standard TRIzol extraction: free RNA and the fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice, particularly in colonies of Cc2d1a (+/−) mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm, both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here, we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA. Full article

Recently, we described the alteration of six miRNAs in the serum of autistic children, their fathers, mothers, siblings, and in the sperm of autistic mouse models. Studies in model organisms suggest that noncoding RNAs participate in transcriptional modulation pathways. Using mice, approaches to alter the amount of RNA in fertilized eggs enable in vivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study addresses a fundamental question: can the transfer of RNA content from sperm to eggs result in changes in phenotypic traits, such as autism? To explore this, we used sperm RNA from a normal father but with autistic children to create mouse models for autism. Here, we induced, in a single step by microinjecting sperm RNA into fertilized mouse eggs, a transcriptional alteration with the transformation in adults of glial cells into cells affected by astrogliosis and microgliosis developing deficiency disorders of the ‘autism-like’ type in mice born following these manipulations. Human sperm RNA alters gene expression in mice, and validates the possibility of non-Mendelian inheritance in autism. Full article

Mitochondria are subcontractors dedicated to energy production within cells. In human mitochondria, almost all mitochondrial proteins originate from the nucleus, except for 13 subunit proteins that make up the crucial system required to perform ‘oxidative phosphorylation (OX PHOS)’, which are expressed by the mitochondria’s self-contained DNA. Mitochondrial DNA (mtDNA) also encodes 2 rRNA and 22 tRNA species. Mitochondrial DNA replicates almost autonomously, independent of the nucleus, and its heredity follows a non-Mendelian pattern, exclusively passing from mother to children. Numerous studies have identified mtDNA mutation-related genetic diseases. The consequences of various types of mtDNA mutations, including insertions, deletions, and single base-pair mutations, are studied to reveal their relationship to mitochondrial diseases. Most mitochondrial diseases exhibit fatal symptoms, leading to ongoing therapeutic research with diverse approaches such as stimulating the defective OXPHOS system, mitochondrial replacement, and allotropic expression of defective enzymes. This review provides detailed information on two topics: (1) mitochondrial diseases caused by mtDNA mutations, and (2) the mechanisms of current treatments for mitochondrial diseases and clinical trials. Full article

Mendelian heredity is the cornerstone of plant breeding and has been used to develop new varieties of plants since the 19th century. However, there are several breeding cases, such as cytoplasmic inheritance, methylation, epigenetics, hybrid vigor, and loss of heterozygosity (LOH), where Mendelian heredity is not applicable, known as non-Mendelian heredity. This type of inheritance can be influenced by several factors besides the genetic architecture of the plant and its breeding potential. Therefore, exploring various non-Mendelian heredity mechanisms, their prevalence in plants, and the implications for plant breeding is of paramount importance to accelerate the pace of crop improvement. In this review, we examine the current understanding of non-Mendelian heredity in plants, including the mechanisms, inheritance patterns, and applications in plant breeding, provide an overview of the various forms of non-Mendelian inheritance (including epigenetic inheritance, cytoplasmic inheritance, hybrid vigor, and LOH), explore insight into the implications of non-Mendelian heredity in plant breeding, and the potential it holds for future research. Full article

The origin of genes is one of the most enigmatic events in the origin of life. It has been suggested that noncoding (nc) RNA was probably a precursor in the formation of the first polypeptide, and also at the origin of the first manifestation of life and genes. ncRNAs are also becoming central for understanding gene expression and silencing. Indeed, before the discovery of ncRNAs, proteins were viewed as the major molecules in the regulation of gene expression and gene silencing; however, recent findings suggest that ncRNA also plays an important role in gene expression. Reverse transcription of RNA viruses and their integration into the genome of eukaryotes and also their relationship with the ncRNA suggest that their origin is basal in genome evolution, and also probably constitute the first mechanism of gene regulation. I am to review the different roles of ncRNAs in the framework of gene evolution, as well as the importance of ncRNAs and viruses in the epigenesis and in the non-Mendelian model of heredity and evolution. Full article