A5082302395- RNA modifications and cancer
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Computational Drug Discovery Methods
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Prion Diseases and Protein Misfolding
- Cancer-related gene regulation
- Virus-based gene therapy research
- Fibroblast Growth Factor Research
- Receptor Mechanisms and Signaling
- Biochemical and Molecular Research
- Autism Spectrum Disorder Research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Bacteriophages and microbial interactions
- Adenosine and Purinergic Signaling
- Viral Infectious Diseases and Gene Expression in Insects
Spanish National Cancer Research Centre
2018-2025
Centro de Investigación del Cáncer
2023
Highlights•(PR)n peptides trigger a generalized accumulation of polysome-unbound r-proteins•(PR)n-resistant cells present low rates ribosome biogenesis•mTOR inhibition or MYC depletion increases resistance to (PR)n peptides•(PR)97 expression accelerates aging in mice, which is alleviated by rapamycinSummaryNucleolar stress (NS) has been associated with age-related diseases such as cancer neurodegeneration. To investigate how NS triggers toxicity, we used arginine-rich some neurodegenerative...
The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting cell cycle arrest interruption of ribosomal activity, critical factors aging cancer. In this study, we identified described the pivotal role RNA-binding protein (RBP) HNRNPK ribosome dynamics. We developed vitro model endogenous overexpression vivo mouse ubiquitous overexpression. These models showed disruptions translation caused...
The tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated human osteosarcoma cell line, which allows for the inducible of an EGFP fusion TAR DNA-binding protein 43 (TDP-43), has been linked neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led accumulation aggregates and limited viability U2OS. Using conducted chemical screen library that included...
Summary Nucleolar stress (NS) has been associated to several age-related diseases such as cancer or neurodegeneration. To investigate the mechanisms of toxicity triggered by NS, we here used (PR)n arginine-rich peptides that are found in patients some neurodegenerative diseases. Although these accumulate at nucleoli and generate how this translates into cellular is poorly understood. We reveal whereas expression leads an overall decrease protein abundance, occurs concomitant with...
ABSTRACT Due to their capability transport chemicals or proteins into target cells, cell-penetrating peptides (CPPs) are being developed as therapy delivery tools. However, and despite interesting properties, arginine-rich CPPs often show toxicity for reasons that remain poorly understood. Using a (PR)n dipeptide repeat has been linked amyotrophic-lateral sclerosis (ALS) model of an CPP, we here the presence leads generalized displacement RNA- DNA-binding from chromatin mRNA. Accordingly,...
Background: Protein biogenesis is a complex multistep process involving nucleoli and ribosomes. Aberrations in any step could lead to alterations protein output. hnRNP K an RNA binding (RBP) that nascent RNAs into mature mRNAs we found its overexpression results nuclear nucleolar abnormalities, decrease transcription potentially promotes imbalance ribosome biogenesis, leading translation. Aims: We aim elucidate how dysregulation impact on HSC biology. Methods: To study the of vivo, developed...
Abstract The nucleolus is a dynamic structure where ribosome subunits are produced. Indeed, nucleoli respond to any change in cellular homeostasis by altering the rate of biogenesis, thus working as stress sensor. Therefore, an imbalance biogenesis promotes changes morphology and function can evoke nucleolar response. Changes composition impair have been described stress, mechanism related aging cancer. Here, we show role RNA binding protein Hnrnpk dynamics function. ribonucleoprotein charge...
ABSTRACT The tetracycline repressor (tetR)-regulated system is a widely used tool to specifically control gene expression in mammalian cells. Based on this system, we generated human osteosarcoma cell line which allows for inducible of an EGFP-fusion the TAR DNA-binding protein 43 (TDP-43), has been linked neurodegenerative diseases. Consistent with previous findings, TDP-43 overexpression led accumulation aggregates and limited viability U2OS. Using conducted chemical screen library that...