Biology subjects

Rassoulzadegan, M.

Publications and source records attributed to Rassoulzadegan, M..

7 recordsLinked to original sources

bioRxiv2024

Head trauma impairs HPA-axis functions by increased R-loop structure and shortens telomeres

Traumatic brain injury (TBI) causes inflammation, one of the main causes of cellular aging. Telomere repeat-containing RNA (TERRA) hybridizes to telomere regions, forming R-loop structures and ensuring genome stabilization. Deregulation of R-loop homeostasis leads to genomic instability linked to neurodegenerative diseases and cancer. The hypothalamus-pituitary-adrenal (HPA) axis response is critical to maintaining homeostasis after TBI. We showed that the local increase in the transcription levels of the Crh and Pomc genes, in particular, suggests a defensive response through transcriptional alteration against mild TBI despite the decreased rate in the serum in the chronic phase. Additionally, changes in the transcription levels of TERRA and correlations with hormonal deficits after repetitive mTBI head trauma were observed. Telomere shortening and increased hybridized TERRA levels, especially after repeated mTBI in the chronic phase, suggest a possible disorder of genome stabilization and loss of cellular function in tissues of the hypothalamus, pituitary, and adrenal glands.

genomics↗

bioRxiv2023

From Data to Insights: Machine Learning Empowers Prognostic Biomarker Prediction in Autism

Autism Spectrum Disorder (ASD) poses significant challenges to society and science due to its impact on communication, social interaction, and repetitive behaviour patterns in affected children. The Autism and Developmental Disabilities Monitoring (ADDM) Network continuously monitors ASD prevalence and characteristics. In 2020, ASD prevalence was estimated at one in 36 children, with higher rates than previous estimates. This study focuses on ongoing ASD research conducted by Erciyes University. Serum samples from 45 ASD patients and 21 unrelated control participants were analysed to assess the expression of 372 microRNAs (miRNAs). Six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) exhibited significant downregulation in all ASD patients compared to healthy controls. The current study endeavours to identify dependable diagnostic biomarkers for ASD, addressing the pressing need for non-invasive, accurate, and cost-effective diagnostic tools, as current methods are subjective and time intensive. A pivotal discovery in this study is the potential diagnostic value of miR-126-3p, offering the promise of earlier and more accurate ASD diagnoses, potentially leading to improved intervention outcomes. Leveraging machine learning, such as the K-nearest neighbours (KNN) model, presents a promising avenue for precise ASD diagnosis using miRNA biomarkers.

genomics↗

bioRxiv2023

RNA activities of trans species: RNA from the sperm of the father of an autistic child programs glial cells and behavioral disorders in mice.

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 invivo intervention at an early stage of development. Noncoding RNAs are very numerous in spermatozoa. Our study aims to address 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 utilized RNA from the sperm of a father with autistic children and microinjected it into fertilized mouse eggs, thus creating mouse models for autism. Here, we induced in a single step by microinjection of sperm RNA into fertilized eggs the transformation of glial cells into cells capable of developing `autism-like` disorders in mice born from these alterations.

animal behavior and cognition↗

bioRxiv2023

Experimental alteration of the microRNA profile of the mouse embryo: heritable phenotypes in the adult

We previously identified a unique genetic feature of Autism Spectrum Disorder (ASD) in human patients and established mouse models, namely the low to very low level of six microRNAs, miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p and miR-499a-5p. We attempted to interfere experimentally with the expression in the mouse of two of them, miR19a-3p and miR499a-5p by microinjecting into the one-cell embryo either the complementary sequence or an excess of the microRNA. Both approaches resulted in low levels in the somatic tissues and sperm of the targeted microRNAs (nascent) and their pri and pre precursors. The altered miRNA profiles were inherited by progenies of crosses with untreated partners together with behavior alterations partly characteristic of ASD patients and animal models. An excess of miRNA in the eggs leads to a specific downregulation, we propose variations of single-stranded miRNA, as effectors of its own transcription in eukaryotes.

molecular biology↗

bioRxiv2022

Progressive decline in the levels of six miRNAs from parents to children in autism

The growing burden of a gradual increase in births of children with autism has placed it at the center of the concerns of major laboratories. We have previously detected a decrease in the levels of six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) in parents and their children inherited at a lower level. Here, we suggest that down-regulation of each of these six miRNAs inherited from parents contributes to the development of children with autism. We compare their levels of distribution in each family between the autistic child and siblings. We find that the distribution of levels of these miRNAs in siblings (undiagnosed as autism) is not always higher than in autistic children, but it is at varying levels. These data support a model in which autistic behavior relies on low levels of the six miRNAs expressed in children potentially associated with autistic syndrome (ASD). The intimate link between miRNAs levels and behavioral characteristics suggests possibilities for understanding the basic circuitry involved in autism and thus advancing partial knowledge of brain functions. An early diagnosis of autism helps provide children an environment conducive to their development. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/512859v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@176d6f4org.highwire.dtl.DTLVardef@11a4ebforg.highwire.dtl.DTLVardef@280f67org.highwire.dtl.DTLVardef@b3659_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2021

Accumulation of lncRNAs/DNA hybrid reveals RNase HII transcripts down-regulation in psoriasis.

Long functional non-coding RNAs (lncRNAs) have been in the limelight in aging research because short telomeres are associated with higher levels of TERRA (Telomeric Repeat containing RNA). The genomic instability caused in Immune-mediated inflammatory diseases (IMID) especially in patients with psoriasis, which lead to short telomeres in psoriasis lesions, is a mechanism leading to cell aging. Research on the fraction of TERRA in hybrid with DNA offers avenues for new strategies. Skin samples were fractionated to obtain the RNA associated with DNA as a R-loop structure. TERRA analysis was performed by RT-qPCR and RNA-seq analysis. The higher amount of TERRA levels attached with each chromosome end was found with psoriasis patients. The increased levels of TERRA linked with telomeres correlate with the decrease in the RNase-HII transcript which means the unresolved DNA/RNA hybrids may ultimately facilitate the formation of skin lesions. LncRNAs have multiple molecular functions, including the regulation of heterochromatin, which controls genome stability and epigenome shaping and may be used as a trans-generational prognostic marker in patients with psoriasis.

molecular biology↗

bioRxiv2020

DNA-RNA hybrid (R-loop): from a unified picture of the mammalian telomere to the genome-wide

Local three-stranded DNA-RNA hybrid regions of the genomes (R-loops) have been detected either by binding of a monoclonal antibody (DRIP assay) or by enzymatic recognition by RNaseH. Such a structure has been postulated for the mouse and human telomeres, clearly suggested by the identification of the complementary RNA TERRA. It was, however, evidenced by DRIP exclusively in human cancer and not in normal human nor in any mouse cell. Based on the observation that in several fractionation procedures, DNA-RNA hybrids copurify with double-stranded DNA, we developed a preparative approach that allows detection of stable DNA-RNA triplexes in a complex genome, their physical isolation and their RNA nucleotide sequence. We then define in the normal mouse and human genomes the notion of terminal R-loop complexes including TERRA molecules synthesized from local promoters of every chromosome. In addition to the telomeric structures since, the finding of the RNA peak, applied in addition to the whole murine sperm genomes, has highlighted a reproducible profile of the R-loop complexes from entire genome suggesting a defined profile for a future generation.

genetics↗