A5082645394- Chromosomal and Genetic Variations
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Genomics and Phylogenetic Studies
- Cytokine Signaling Pathways and Interactions
- Trypanosoma species research and implications
- Plant Virus Research Studies
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Protein Tyrosine Phosphatases
- Research on Leishmaniasis Studies
- Genomic variations and chromosomal abnormalities
- HIV Research and Treatment
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- DNA and Nucleic Acid Chemistry
- Insect symbiosis and bacterial influences
- Ubiquitin and proteasome pathways
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- Biosensors and Analytical Detection
- Biochemical and Molecular Research
Instituto de Parasitología y Biomedicina "López - Neyra"
2010-2025
Consejo Superior de Investigaciones Científicas
2012-2025
National Academies of Sciences, Engineering, and Medicine
2025
Mater Research
2015-2023
The University of Queensland
2014-2023
Western General Hospital
2020-2023
University of Edinburgh
2020-2023
Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
2017-2023
Queen Mary University of London
2022
Praxis (United States)
2022
Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source of genotypic variation among neurons. As neurogenic niche, the hippocampus supports pronounced L1 activity. However, basal parameters and biological impact L1-driven mosaicism remain unclear. Here, we performed single-cell retrotransposon capture sequencing (RC-seq) on individual human hippocampal neurons glia, as well cortical An estimated 13.7 somatic insertions occurred per neuron carried sequence hallmarks...
LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize cells that will contribute their material to subsequent generations. Heritable insertions may therefore arise germ pluripotent embryonic cells, prior germline specification, yet the frequency predominant developmental timing such events remain unclear. Here, we applied mouse retrotransposon capture sequencing (mRC-seq) whole-genome (WGS) pedigrees...
The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity hallmark cancer, has been described numerous human malignancies. We previously employed capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with hepatitis B C virus identified variants responsible for activating oncogenic pathways. Here, we have applied RC-seq whole-genome (WGS) an Abcb4...
A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing HEK293T cells with SARS-CoV-2 and do not find virus integrated genome. By examining ONT data from separate cultivars, completely resolve 78 L1 insertions...
Abstract Retrotransposons are mobile DNA sequences duplicated via transcription and reverse of an RNA intermediate. Cis -regulatory elements encoded by retrotransposons can also promote the adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 only some neuronal lineages or therein neurodevelopmental gene expression. Here we report programmed activation SOX6, a factor critical for parvalbumin (PV)...
LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells detected endogenous retrotransposition vitro. We then RC-seq matched blood samples 19 patients identified 88 tumor-specific insertions. In one tumor, an intronic de novo...
With the ongoing COVID-19 (Coronavirus Disease 2019) pandemic, caused by novel coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), there is a need for sensitive, specific, and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves detection viral RNA using RT-qPCR (quantitative reverse transcription PCR), with many commercial kits now available this purpose. However, these expensive, supply such in...
L1Tc is a non-LTR LINE element from Trypanosoma cruzi that encodes its transposition machinery and bears an internal promoter. Herewith, we report the identification of in vitro active hepatitis delta virus-like ribozyme located first 77 nt at 5′-end mRNA (L1TcRz). The data presented show L1TcRz has co-transcriptional function. Using gel-purified uncleaved RNA transcripts, indicate kinetics self-cleaving, magnesium-dependent reaction, fits to two-phase decay curve. cleavage point identified...
Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation monomeric units constituting young mouse promoters. Locus-specific dynamics during development may therefore elucidate explain spatiotemporal niches endogenous but remain unresolved. Here, we interrogate efficiency fate source (donor) L1s, identified as mobile...
The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these either by disrupting their structures or blocking interaction cellular factors may seriously compromise HIV-1 viability. aptamers are amongst most promising synthetic molecules able to interact genomes. However, aptamer shortening up minimal active domain is usually necessary for scaling...
The 22q11.2 deletion syndrome (22qDS) is a human disorder where the majority of clinical manifestations originate during embryonic development. 22qDS caused by microdeletion in one chromosome 22, including DGCR8, an essential gene for microRNA (miRNA) production. However, impact DGCR8 hemizygosity on development still unclear. In this study, we generated two pluripotent cell models containing single functional allele to elucidate its role early DGCR8+/- stem cells (hESCs) showed increased...
Abstract To improve ex vivo gene therapy strategies involving hematopoietic stem and progenitor cells (HSPCs), we propose a novel knock-in strategy (named KI-Ep) aiming to achieve transgene regulation of the inserted cassette through acquisition naturally occurring epigenetic marks. Based on this hypothesis, selected CX3CR1 (a myeloid-specific presenting poised histone signature primitive HSPCs) as safe harbor generate KI-Ep HSPCs. We demonstrated that, unlike expression pattern achieved...
Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements prevent element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome sequencing 38 bulk miPSC lines reprogrammed from 10 parental types, 18 single-cell clones. While single nucleotide...
The retrotransposon LINE-1 (L1) is a significant source of endogenous mutagenesis in humans. In each individual genome, few retrotransposition-competent L1s (RC-L1s) can generate new heritable L1 insertions the early embryo, primordial germ line, and cells. retrotransposition also occur neuronal lineage cause somatic mosaicism. Although DNA methylation mediates promoter repression, temporal pattern applied to RC-L1s during neurogenesis unclear. Here, we identified de novo insertion human...
Abstract The GTPase RhoA is a downstream target of heterotrimeric G13 proteins and plays key roles in cell migration invasion. Here, we show that expression human melanoma cells constitutively active, GTPase-deficient Gα13 form (Gα13QL) or lysophosphatidylcholine (LPC)-promoted signaling through Gα13-coupled receptors led to blockade chemokine-stimulated activation invasion was rescued by active RhoA. Melanoma expressing Gα13QL stimulated with LPC displayed an increase p190RhoGAP activation,...
The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of human genome and continues drive genetic diversity germline pathogenesis. However, spatiotemporal extent biological significance somatic L1 activity are poorly defined virtually unexplored in other primates. From a single lineage active at divergence apes Old World monkeys, successive subfamilies have emerged each descendant primate germline. As revealed by case studies, presently subfamily can also mobilize...
The sequence corresponding to the first 77 nucleotides of L1Tc and NARTc non-LTR retrotransposons from Trypanosoma cruzi is an internal promoter (Pr77) that generates abundant, although poorly translatable, un-spliced transcripts. It has been recently described L1TcRz, HDV-like ribozyme, resides within 5'-end RNA retrotransposons. Remarkably, same L1Tc/NARTc elements comprise both Pr77 L1TcRz. L1TcRz cleaves on 5'-side +1 nucleotide element insuring ribozyme functions travel with transposon...
Hepatitis Delta Virus (HDV)-like ribozymes have recently been found in many mobile elements which they take part a mechanism that releases intermediate RNAs from cellular co-transcripts. L1Tc Trypanosoma cruzi is one of the such ribozyme located. It lies so-called Pr77-hallmark, conserved region shared by retrotransposons belonging to trypanosomatid L1Tc/ingi clade. The wide distribution Pr77-hallmark detected renders potential catalytic activity these worthy study: their might contribute...