Publications by authors named "Sara Pico"
Aging is the major risk factor for most human diseases and represents a major socioeconomical challenge for modern societies. Despite its importance, the process of aging remains poorly understood. Epigenetic dysregulation has been proposed as a key driver of the aging process.
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- - Alternative splicing includes microexons in neuronal proteins, which are often linked to neurodevelopmental disorders, including autism spectrum disorder (ASD).
- - A specific 24-nucleotide microexon in the RNA-binding protein CPEB4, previously shown to be less included in individuals with ASD, plays a critical role in regulating gene expression linked to neurodevelopment.
- - The study finds that this microexon helps maintain the flexible regulation of CPEB4 during neuronal activation by preventing its aggregation, allowing it to switch from repressing to activating translation of genes.
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- Aging is the main cause of many diseases and is a big challenge for society because we don't fully understand how it works.
- A specific change in how our genes are controlled, called H3K9me3, might play a big role in aging, but we don't know exactly how yet.
- Research using special mice showed that losing H3K9me3 leads to faster aging, less lifespan, and health problems, suggesting that fixing epigenetic changes could help slow down aging.
We have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying the highly prevalent PAH variant c.1066-11G>A. This variant creates an alternative 3' splice site, leading to the inclusion of 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 of the protein.
View Article and Find Full Text PDFSeveral premature aging mouse models have been developed to study aging and identify interventions that can delay age-related diseases. Yet, it is still unclear whether these models truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported mouse models of premature aging (Ercc1, LAKI, Polg, and Xpg).
View Article and Find Full Text PDFThe induction of cellular reprogramming via expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can drive dedifferentiation of somatic cells and ameliorate age-associated phenotypes in multiple tissues and organs. However, the benefits of long-term in vivo reprogramming are limited by detrimental side-effects. Here, using complementary genetic approaches, we demonstrated that continuous induction of the reprogramming factors in vivo leads to hepatic and intestinal dysfunction resulting in decreased body weight and contributing to premature death (within 1 week).
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- Schizophrenia (SCZ) is influenced by genetic and environmental factors that may disrupt the regulation of gene expression, with the CPEB4 protein identified as a key player in both SCZ and autism spectrum disorder (ASD).
- Research revealed that SCZ individuals showed reduced usage of a specific microexon in CPEB4, which correlated with lower levels of targeted genes associated with SCZ, particularly in those not taking antipsychotics.
- Experimental findings in mice with altered CPEB4 expression support the link between aberrant splicing of CPEB4 and disrupted gene expression related to SCZ, suggesting a potential mechanism for the disorder.
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- Huntington's disease (HD) is a hereditary neurodegenerative disorder with no current disease-modifying treatments, but researchers are investigating gene-silencing therapies and potential molecular mechanisms for drug targets.
- An analysis of protein levels in HD patients and mouse models showed increased CPEB1 and decreased CPEB4, leading to significant changes in the transcriptome that affect neurodegeneration-associated genes.
- Notably, a deficiency in thiamine and its active form, TPP, was observed in HD patients, and high-dose biotin and thiamine treatment in mouse models improved symptoms and could offer a new therapeutic option for HD.
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- Correction of mis-splicing events is being explored as a therapeutic strategy for neurological diseases like spinal muscular atrophy and Huntington's disease, which arise from splicing-related mutations.
- Next-generation RNA sequencing has enabled the detailed study of mis-spliced genes in diseases, although challenges exist in analyzing brain tissue due to cell loss and inflammation in neurodegenerative conditions.
- The study utilized intersect-RNA-seq to identify common mis-splicing patterns in Huntington's disease, leading to potential new therapeutic targets related to the disease's progression.
Article Synopsis
- Common genetic factors contribute to autism spectrum disorder (ASD) through risk gene variants that have minimal individual effects, alongside environmental influences that disrupt neurodevelopment.
- Cytoplasmic polyadenylation element binding proteins (CPEB1-4) are crucial for regulating the translation of specific mRNAs during development, and CPEB4 is particularly linked to many high-confidence ASD risk genes.
- In individuals with idiopathic ASD, imbalances in CPEB4 transcripts lead to shorter poly(A)-tails and reduced expression of ASD risk gene proteins, and similar disruptions in mice produce ASD-like characteristics, implicating CPEB4 as a key regulator in ASD.
Polycomb group (PcG) proteins play important roles in regulating developmental phase transitions in plants; however, little is known about the role of the PcG machinery in regulating the 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 in the repression of microRNA156 (miR156). Loss of AtBMI1 function leads to the up-regulation of the primary transcript of MIR156A and MIR156C at the time the levels of miR156 should decline, resulting in an extended juvenile phase and delayed flowering.
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