A5074664526- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA regulation and disease
- Glioma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Viral Infections and Immunology Research
- Autism Spectrum Disorder Research
- RNA Interference and Gene Delivery
- Protein Kinase Regulation and GTPase Signaling
- Cancer Genomics and Diagnostics
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Autophagy in Disease and Therapy
- Nuclear Receptors and Signaling
Josep Carreras Leukaemia Research Institute
2020-2025
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
2020-2025
Hospital Universitari Germans Trias i Pujol
2023
Institut d'Investigació Biomédica de Bellvitge
2008-2021
Ajuntament de L’Hospitalet
2017
Bellvitge University Hospital
2012-2015
Western General Hospital
2005-2008
Medical Research Council
2005-2008
Consejo Superior de Investigaciones Científicas
2001-2008
Institut d'Investigacions Biomèdiques de Barcelona
2008
We recently found that hnRNP A1, a protein implicated in many aspects of RNA processing, acts as an auxiliary factor for the Drosha-mediated processing microRNA precursor, pri-miR-18a. Here, we provide mechanism by which A1 regulates this event. show binds to loop pri-miR-18a and induces relaxation at stem, creating more favorable cleavage site Drosha. approximately 14% all pri-miRNAs have highly conserved loops, predict act landing pads trans-acting factors influencing miRNA processing. In...
Significance The molecular mechanisms used by noncoding RNAs to regulate gene expression are largely unknown. We have discovered a previously unidentified regulatory phenomenon underlying the transcriptional activation of intermediate filament protein vimentin. This regulation involves participation uncharacterized head-to-head antisense transcript that forms part hybrid DNA:RNA structure known as R loop. loops been focus recent research regarding their unexpected involvement in regulation....
One of the hallmarks cancer is disruption gene expression patterns. Many molecular lesions contribute to this phenotype, and importance aberrant DNA methylation profiles increasingly recognized. Much research effort in area has examined proximal promoter regions epigenetic alterations at other loci are not well characterized. Using whole genome bisulfite sequencing examine uncharted epigenome, we identify a type far-reaching alteration cells distal regulatory sequences described as...
Abstract Newly growing evidence highlights the essential role that epitranscriptomic marks play in development of many cancers; however, little is known about and implications altered epitranscriptome deposition prostate cancer. Here, we show transfer RNA N 7 -methylguanosine (m G) transferase METTL1 highly expressed primary advanced tumours. Mechanistically, find depletion causes loss m G tRNA methylation promotes biogenesis a novel class small non-coding RNAs derived from 5'tRNA fragments....
hnRNP A1 is a nucleocytoplasmic shuttling protein that involved in many aspects of mRNA metabolism. We have previously shown activation the p38 stress-signaling pathway mammalian cells results both hyperphosphorylation and cytoplasmic accumulation A1, affecting alternative splicing regulation vivo. Here we show stress-induced occurs discrete phase-dense particles, stress granules (SGs). Interestingly, mRNA-binding activity required for phosphorylation localization to SGs. also these effects...
Significance Long noncoding RNAs (lncRNAs) are starting to be recognized as critical molecules for cellular transformation, although only a few candidates have so far been characterized. Here we report that TP53TG1 is an lncRNA the correct response of p53 DNA damage. The cancer growth suppressor features linked its ability block tumorigenic activity RNA binding protein YBX1. methylation-associated silencing produces aggressive tumors resistant death when DNA-damaging agents and small...
Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence RNA modification landscapes in so-called epitranscriptome. Here, we report human glioma cells undergo DNA methylation-associated epigenetic silencing NSUN5, a candidate methyltransferase for 5-methylcytosine. In setting, NSUN5 exhibits tumor-suppressor characteristics vivo models. We also found loss generates an unmethylated status at...
The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population small. There need to discover potential actionable lesions, which end, non-conventional pathways, such as RNA editing, are worth exploring. Herein we show that adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification non-small cell lines and primary tumors association with higher levels corresponding...
RNA modifications are important regulators of transcript activity and an increasingly emerging body data suggests that the epitranscriptome its associated enzymes altered in human tumors.
Heterogenous nuclear ribonucleoprotein (hnRNP) A1 is an alternative splicing factor that mainly nuclear, although it shuttles rapidly between and cytoplasmic compartments. Cells stressed by osmotic shock (OSM) activate the mitogen-activated protein kinase 3/6 -p38 signaling pathway, which in turn results accumulation of hnRNP cytoplasm. This effect modulates regulation vivo correlates with increased phosphorylation. We have characterized molecular mechanism involved NIH 3T3 cells subjected...
Human ras genes play central roles in coupling extracellular signals with complex intracellular networks controlling proliferation, differentiation, and apoptosis, among others processes. c-H-ras pre-mRNA can be alternatively processed into two mRNAs due to the inclusion or exclusion of alternative exon IDX; this renders proteins, p21H-Ras p19H-RasIDX, which differ only at carboxy terminus. Here, we have characterized some cis-acting sequences trans-acting factors regulating IDX splicing. A...
Rett syndrome (RTT) is the second leading cause of mental impairment in girls and currently untreatable. RTT caused, more than 95% cases, by loss-of-function mutations methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved RTT: glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity deregulated Mecp2-knockout (KO) mice models, SB216763, specific inhibitor, able to alleviate clinical symptoms with consequences at cellular levels. In vivo, inhibition...
One largely unknown question in cell biology is the discrimination between inconsequential and functional transcriptional events with relevant regulatory functions. Here, we find that oncofetal HMGA2 gene aberrantly reexpressed many tumor types together its antisense transcribed pseudogene RPSAP52. RPSAP52 abundantly present cytoplasm, where it interacts RNA binding protein IGF2BP2/IMP2, facilitating to mRNA targets, promoting their translation by mediating recruitment on polysomes enhancing...
Significance Defects in transfer RNA (tRNA) modifications occur human pathologies such as cancer; however, how these alterations contribute to the disease is poorly understood. One example tumor-specific hypomodification of position 37 tRNA Phe , which was first described 45 y ago, although its cause and consequences have remained unknown. Here we report that due promoter CpG island hypermethylation-associated transcriptional silencing TYW2, a key enzyme synthesis wybutosine derivatives....
Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A. Here we detect plitidepsin decreases de novo cap-dependent of SARS-CoV-2 and non-viral RNAs but affects less than 13% host proteome, thus preserving cellular viability. In response to plitidepsin, cells upregulate EIF2AK3 proteins reduce translation, also support proteostasis via ribosome synthesis cap-independent by eIF4G2 IGF2BP2. While inhibits cap- or internal entry...