The sphingolipid anteome: implications for evolution of the sphingolipid metabolic pathway

FEBS Letters, Год журнала: 2022, Номер 596(18), С. 2345 - 2363

Опубликована: Июль 28, 2022

Modern cell membranes contain a bewildering complexity of lipids, among them sphingolipids (SLs). Advances in mass spectrometry have led to the realization that number and combinatorial including SLs, is much greater than previously appreciated. SLs are generated de novo by four enzymes, namely serine palmitoyltransferase, 3-ketodihydrosphingosine reductase, ceramide synthase dihydroceramide Δ4-desaturase 1. Some these enzymes depend on availability specific substrates cofactors, which themselves supplied other complex metabolic pathways. The evolution poorly understood likely depends co-evolution pathways supply essential reaction components. Here, we introduce concept 'anteome', from Latin ante ('before') describe network ('omic') must converged order for co-evolve permit SL synthesis. We also suggest current origin life evolutionary models lack appropriate experimental support explain appearance this pathway its anteome.

Язык: Английский

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Pseudogenes in Cancer: State of the Art

Cancers, Год журнала: 2023, Номер 15(16), С. 4024 - 4024

Опубликована: Авг. 8, 2023

Pseudogenes are duplicates of protein-coding genes that have accumulated multiple detrimental alterations, rendering them unable to produce the protein they encode. Initially disregarded as "junk DNA" due their perceived lack functionality, research on biological roles has been hindered by this assumption. Nevertheless, recent focus shifted towards these molecules abnormal expression in cancer phenotypes. In review, our objective is provide a thorough overview current understanding pseudogene formation, mechanisms governing expression, and may play promoting tumorigenesis.

Язык: Английский

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Unveiling the regulatory potential of the non-coding genome: Insights from the Human Genome Project to precision medicine

Genes & Diseases, Год журнала: 2025, Номер unknown, С. 101652 - 101652

Опубликована: Апрель 1, 2025

Язык: Английский

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Uncovering the Contrasting Binding Behavior of Plant Flavonoids Fisetin and Morin Having Subsidiary Hydroxyl Groups (−OH) with HRAS1 and HRAS2 i-Motif DNA Structures: Decoding the Structural Alterations and Positional Influences

ACS Omega, Год журнала: 2023, Номер 8(33), С. 30315 - 30329

Опубликована: Авг. 7, 2023

Research on the interactions of naturally existing flavonoids with various noncanonical DNA such as i-motif (IM) structures is helpful in comprehending molecular basis binding mode well providing future direction for application and invention novel effective therapeutic drugs. IM have been identified prospective anticancer targets, are smaller molecules a variety health-promoting attributes, including activities. The extensive investigation comprising series techniques reveals contrasting behavior fisetin morin structures. We discovered that structural alterations hydroxyl groups located at different places aromatic rings influence flavonoid's reactivity. This minor alteration appears to be critical morin's capacity interact differentially HRAS1 HRAS2 DNA. Hence, an efficient ligand considered exploration opens up possibility employing strategy regulation gene expression cancerous cells. Our finding also flavonoid-mediated specific interaction while pointing toward tangible strategies drug discovery other essential cellular functions.

Язык: Английский

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Gene editing of non-coding regulatory DNA and its application in crop improvement

Journal of Experimental Botany, Год журнала: 2023, Номер 74(19), С. 6158 - 6175

Опубликована: Авг. 7, 2023

Abstract The development of the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has provided precise and efficient strategies to edit target genes generate transgene-free crops. Significant progress been made in editing protein-coding genes; however, studies on non-coding DNA with regulatory roles lags far behind. Non-coding DNAs, including those which can be transcribed into long RNAs (lncRNAs), miRNAs, together cis-regulatory elements (CREs), play crucial regulating plant growth development. Therefore, combination CRISPR/Cas technology great potential novel alleles that affect various agronomic traits crops, thus providing valuable genetic resources for crop breeding. Herein, we review recent advances DNA, attempts improvement, application tools modulating DNA. Finally, existing problems, possible solutions, future applications gene modern breeding practice are also discussed.

Язык: Английский

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Hereditary transthyretin amyloidosis: a myriad of factors that influence phenotypic variability

Journal of Neurology, Год журнала: 2024, Номер 271(9), С. 5746 - 5761

Опубликована: Июнь 22, 2024

Hereditary transthyretin-related amyloidosis (ATTRv amyloidosis) is a rare and progressively debilitating disease characterized by the deposition of transthyretin (TTR) amyloid fibrils in various organs tissues, most commonly heart peripheral nerves. This pathological can lead to significant organ dysfunction and, ultimately, failure. ATTRv exhibits broad range clinical presentations, from purely neurological symptoms cardiac manifestations, as well mixed phenotypes which result both implications. wide phenotypical spectrum realistically challenges diagnosis prognosis, especially individuals without or with an unknown family history. Multiple factors are thought contribute this variability, including genetic, epigenetic, even environmental influences. Understanding these crucial, they significantly affect expression progression. review aims summarize each contributing factors, help elucidate current knowledge on variability amyloidosis.

Язык: Английский

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PRKCE non-coding variants influence on transcription as well as translation of its gene

RNA Biology, Год журнала: 2022, Номер 19(1), С. 1115 - 1129

Опубликована: Окт. 26, 2022

Untranslated regions of the gene play a crucial role in expression regulation at mRNA and protein levels. Mutations UTRs impact by altering transcription factor binding, transcriptional/translational efficacy, miRNA-mediated regulation, secondary structure, ribosomal translocation, stability. PKCε, serine/threonine kinase, is aberrantly expressed numerous diseases such as cardiovascular disorders, neurological cancers; its probable cause unknown. Therefore, current study, influence PRKCE 5'-and 3'UTR variants was explored for their potential on translation through several bioinformatics approaches. UTR data obtained different databases initially evaluated regulatory function. Variants with function were then studied effect binding factors (TF) miRNAs, well structure. Study outcomes indicated 73 5'UTR 17 out 376. introduced AP1 sites promoted transcription. Four circular increasing translational efficacy. A region position 45,651,564 to 45,651,644 found where readily influenced miRNA-PRKCE binding. The study further highlighted PKCε-regulated feedback loop mechanism that induces activity TFs, promoting provides foundations experimentation understand these variants' diseases. These can also serve genetic markers diseases' diagnoses after validation cell population

Язык: Английский

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Molecular role of non-exonic variants in CALPAIN 10 gene in polycystic ovarian syndrome in Saudi women

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Дек. 27, 2023

Non-diabetic women with polycystic ovarian syndrome (PCOS) often have abnormal insulin regulation. Calpain 10 (CALP10) is a biomarker of type 2 diabetes mellitus, some its single-nucleotide polymorphisms (SNPs) influencing PCOS development.

Язык: Английский

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Regional random mutagenesis driven by multiple sgRNAs and diverse on-target genome editing events to identify functionally important elements in non-coding regions

Open Biology, Год журнала: 2024, Номер 14(4)

Опубликована: Апрель 1, 2024

Functional regions that regulate biological phenomena are interspersed throughout eukaryotic genomes. The most definitive approach for identifying such is to confirm the phenotype of cells or organisms in which specific have been mutated removed from genome. This invaluable functional analysis genes with a defined element, protein-coding sequence. By contrast, no platforms established study cis -elements microRNA cluster consisting multiple microRNAs overlap. Whole-genome mutagenesis approaches, as via N -ethyl- -nitrosourea and gene trapping, greatly contributed elucidating function coding genes. These methods almost never induce deletions genomic mutations within narrow region. In other words, clusters cannot be effectively targeted manner. Herein, we novel region-specific random method named CRISPR- transposase-based regional (CTRL-mutagenesis). We demonstrate CTRL-mutagenesis randomly induces diverse target murine embryonic stem cells. Comparative mutants harbouring subtly different same region would facilitate further -element clusters.

Язык: Английский

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Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

Biomolecules, Год журнала: 2022, Номер 12(5), С. 652 - 652

Опубликована: Апрель 29, 2022

Pancreatic cancer (PC) is an aggressive malignancy with a dismal prognosis. To improve patient survival, the development of screening methods for early diagnosis pivotal. Oncogenomic alterations present in tumor tissue are suitable target non-invasive efforts, as they can be detected tumor-derived cells, cell-free nucleic acids, and extracellular vesicles, which several body fluids. Since stool easily accessible source, enables convenient cost-effective sampling, it could utilized these traces. Herein, we explore various oncogenomic changes that have been PC tissue, such chromosomal aberrations, mutations driver genes, epigenetic alterations, differentially expressed non-coding RNA. In addition, briefly look into role altered gut microbiota their possible associations changes. We also review findings genomic patients, potentials challenges future use tools, including combination markers.

Язык: Английский

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