A5076897983- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Pluripotent Stem Cells Research
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Adipose Tissue and Metabolism
- Neurological diseases and metabolism
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- Alcoholism and Thiamine Deficiency
- Birth, Development, and Health
- 3D Printing in Biomedical Research
- Plant Genetic and Mutation Studies
- Biochemical and Molecular Research
- Tissue Engineering and Regenerative Medicine
University of Lausanne
2023-2024
Instituto de Salud Carlos III
2021-2024
Universidad Autónoma de Madrid
2018-2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2021-2024
Centro de Biología Molecular Severo Ochoa
2018-2024
Instituto de Bioquímica Vegetal y Fotosíntesis
2015
Consejo Superior de Investigaciones Científicas
2015
Universidad de Sevilla
2015
Polycomb group (PcG) proteins play important roles in regulating developmental phase transitions plants; however, little is known about the role of PcG machinery transition from juvenile to adult phase. Here, we show that Arabidopsis (Arabidopsis thaliana) B lymphoma Moloney murine leukemia virus insertion region1 homolog (BMI1) POLYCOMB REPRESSIVE COMPLEX1 (PRC1) components participate repression microRNA156 (miR156). Loss AtBMI1 function leads up-regulation primary transcript MIR156A and...
Correction of mis-splicing events is a growing therapeutic approach for neurological diseases such as spinal muscular atrophy or neuronal ceroid lipofuscinosis 7, which are caused by splicing-affecting mutations. Mis-spliced effector genes that do not harbour mutations also good candidate targets in with more complex aetiologies cancer, autism, dystrophies neurodegenerative diseases. Next-generation RNA sequencing (RNA-seq) has boosted investigation global diseased tissue to identify key...
The inclusion of microexons by alternative splicing occurs frequently in neuronal proteins. roles these sequences are largely unknown, and changes their degree associated with neurodevelopmental disorders1. We have previously shown that decreased a 24-nucleotide neuron-specific microexon CPEB4, RNA-binding protein regulates translation through cytoplasmic poly(A) tail length, is linked to idiopathic autism spectrum disorder (ASD)2. Why this required how small its dominant-negative effect on...
Schizophrenia (SCZ) is caused by an interplay of polygenic risk and environmental factors, which may alter regulators gene expression leading to pathogenic misexpression SCZ genes. The CPEB family RNA-binding proteins (CPEB1-4) regulates translation target RNAs (approximately 40% overall genes). We previously identified CPEB4 as a key dysregulated translational regulator in autism spectrum disorder (ASD) because its neuronal-specific microexon (exon 4) mis-spliced ASD brains, causing...
Aging is the major risk factor for most human diseases and represents a socio-economical challenge modern societies. Despite its importance, process of aging remains poorly understood. Epigenetic dysregulation has been proposed as key driver process. Modifications in transcriptional networks chromatin structure might be central to age-related functional decline. A prevalent feature described during overall reduction heterochromatin, specifically marked by loss repressive histone...
The inclusion of microexons by alternative splicing is frequent in neuronal proteins. roles these sequences are most cases unknown, but changes their degree associated with neurodevelopmental diseases. We recently found that the decreased a 24-nucleotide neuron-specific microexon CPEB4, an RNA-binding protein regulates translation through cytoplasmic poly(A) tail length, linked to idiopathic autism spectrum disorder (ASD). Why this required and how small its generate dominant-negative effect...
Altered CPEBs and mRNA polyadenylation lead to thiamine deficiency in the brains of patients mice with Huntington’s disease.
Abstract Several premature aging mouse models have been developed to study and identify interventions that can delay age‐related diseases. Yet, it is still unclear whether these truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported ( Ercc1 , LAKI Polg Xpg ). We estimated (DNAm) age samples using the Horvath clock. The most pronounced increase DNAm could be observed mice, a strain which exhibits deficit nucleotide excision repair....
Summary In vivo reprogramming through the forced expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) has demonstrated great potential for reversing age-associated phenotypes, as combination these transcription factors actively promote cell regeneration rejuvenation in various tissues organs. However, continuous OSKM raised safety concerns due to loss identity, decrease body weight, premature death. Although cyclic short-term or targeted can mitigate some detrimental effects mice, systemic wild...
We have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying highly prevalent PAH variant c.1066-11G>A. This creates an alternative 3' splice site, leading to inclusion 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 protein. Homozygous Pah c.1066-11A mice, with intron 10 sequence variant, accurately recapitulate splicing defect present almost undetectable hepatic activity. They exhibit fur...
SUMMARY In the last decade, cellular reprogramming of fully differentiated cells to pluripotent stem has become great interest. Importantly, by expression Oct4, Sox2, Klf4, and cMyc (OSKM) can ameliorate age-associated phenotypes in multiple tissues extend lifespan progeroid aged wild-type mice. Surprisingly, effects vivo have not been deeply investigated any other model organisms. Here, for first time, we induce C. elegans using a heat-inducible system at developmental adult stages. Similar...
Abstract Age-associated neurodegenerative disorders represent significant challenges due to progressive neuronal decline and limited treatments. In aged mice, partial reprogramming, characterized by pulsed expression of reprogramming factors, has shown promise in improving function various tissues, but its impact on the aging brain remains poorly understood. Here we investigated vivo mature neurons dentate gyrus young mice. Using two different approaches – a neuron-specific transgenic...
ABSTRACT Background Microexons are highly conserved and mostly neuronal-specific 3-27 nucleotide exons, enriched in genes linked to autism spectrum disorders (ASD). We have previously shown decreased inclusion of a neuronal specific 24 bp microexon (exon 4) the translational regulator CPEB4 brains idiopathic ASD cases that this leads aggregation subsequent under-expression multiple high confidence ASD-risk genes. Furthermore, enhanced skipping is also novel etiological mechanism...
<title>Abstract</title> Aging is the major risk factor for most human diseases and represents a socio-economical challenge modern societies. Despite its importance, process of aging remains poorly understood. Epigenetic dysregulation has been proposed as key driver process. Alterations in transcriptional networks chromatin structure might be central to age-related functional decline. A prevalent feature described during overall reduction heterochromatin, specifically marked by loss...
ABSTRACT Schizophrenia (SCZ) is caused by a complex interplay of polygenic risk and environmental factors, which might alter regulators gene expression leading to pathogenic mis-expression SCZ genes. The RNA binding protein family CPEB (CPEB1, CPEB2, CPEB3, CPEB4) regulates the translation target RNAs bearing CPE sequences in their 3’UTR (approximately 40% overall genes). We previously identified CPEB4 as key dysregulated translational regulator autism spectrum disorder (ASD), proving that...
Abstract We have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying highly prevalent PAH variant c.1066-11G>A. This creates an alternative 3’ splice site, leading to inclusion 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 protein. Homozygous Pah c.1066-11A mice, with intron 10 sequence variant, accurately recapitulate splicing defect present almost undetectable hepatic activity. They...
<h3>Background</h3> Although promising gene-silencing therapies are being tested for Huntington's disease (HD), no disease-modifying treatments available. Thus, study of molecular mechanisms underneath <i>Htt</i>-mutation must continue to identify easily druggable targets. Cytoplasmic polyadenylation element binding proteins 1–4 (CPEB1–4) RNA-binding that repress or activate translation CPE-containing transcripts by shortening elongating their poly(A) tail. Alteration CPEB-dependent...