A5040905591- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Cardiomyopathy and Myosin Studies
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Nutrition, Genetics, and Disease
- Immunotherapy and Immune Responses
- Machine Learning in Bioinformatics
- Fungal and yeast genetics research
- Natural Language Processing Techniques
- Molecular Biology Techniques and Applications
- Aging, Health, and Disability
- Archaeological and Historical Studies
- Animal Genetics and Reproduction
- Genetic and phenotypic traits in livestock
- Ubiquitin and proteasome pathways
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- Bladder and Urothelial Cancer Treatments
- Plant and Fungal Interactions Research
- Gender Studies in Language
- Basque language and culture studies
Max Delbrück Center
2019-2025
Universitat Pompeu Fabra
2014-2021
Hospital Del Mar
2015-2017
Evolutionary Genomics (United States)
2014
Deep transcriptome sequencing has revealed the existence of many transcripts that lack long or conserved open reading frames (ORFs) and which have been termed non-coding RNAs (lncRNAs). The vast majority lncRNAs are lineage-specific do not yet a known function. In this study, we test hypothesis they may act as repository for synthesis new peptides. We find large fraction expressed in cells from six different species is associated with ribosomes. patterns ribosome protection consistent...
Genomic studies of endangered species provide insights into their evolution and demographic history, reveal patterns genomic erosion that might limit viability, offer tools for effective conservation. The Iberian lynx (Lynx pardinus) is the most felid a unique example on brink extinction.
Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized transcriptome 880,000 nuclei from 18 control 61 failing, nonischemic human hearts with pathogenic DCM ACM or idiopathic disease. We performed genotype-stratified analyses ventricular cell lineages transcriptional states. The resultant atlas demonstrated distinct...
All species continuously evolve short open reading frames (sORFs) that can be templated for protein synthesis and may provide raw materials evolutionary adaptation. We analyzed the origins of 7,264 recently cataloged human sORFs found most were evolutionarily young had emerged de novo. additionally identified 221 previously missed potentially translated into peptides up to 15 amino acids—all which are smaller than smallest microprotein annotated date. To investigate bioactivity sORF-encoded...
Ribosome profiling (Ribo-Seq) has proven transformative for our understanding of the human genome and proteome by illuminating thousands noncanonical sites ribosome translation outside currently annotated coding sequences (CDSs). A conservative estimate suggests that at least 7000 ORFs are translated, which, first glance, potential to expand number protein CDSs 30%, from ∼19,500 over 26,000 CDSs. Yet, additional scrutiny these raised numerous questions about what fraction them truly produce...
A hallmark of high-risk childhood medulloblastoma is the dysregulation RNA translation. Currently, it unknown whether dysregulates translation putatively oncogenic non-canonical open reading frames (ORFs). To address this question, we performed ribosome profiling 32 tissues and cell lines observed widespread ORF We then developed a stepwise approach using multiple CRISPR-Cas9 screens to elucidate ORFs putative microproteins implicated in survival. determined that lncRNA-ORFs upstream (uORFs)...
The birth of new genes is an important motor evolutionary innovation. Whereas many arise by gene duplication, others originate at genomic regions that did not contain any or copies. Some these newly expressed may acquire coding non-coding functions and be preserved natural selection. However, it yet unclear which the prevalence underlying mechanisms de novo emergence. In order to obtain a comprehensive view this process, we have performed in-depth sequencing transcriptomes four mammalian...
De novo gene origination has been recently established as an important mechanism for the formation of new genes. In organisms with a large genome, intergenic and intronic regions provide plenty raw material transcriptional events to occur, but little is know about how de transcripts originate in more densely-packed genomes. Here, we identify 213 originated Saccharomyces cerevisiae using deep transcriptomics genomic synteny information from multiple yeast species grown two different...
The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this leads to functionally diverse 'specialized ribosomes' still controversial topic. Here, we explore the biological function RPL3L (uL3L), ribosomal protein (RP) paralogue RPL3 (uL3) that exclusively expressed in skeletal muscle and heart tissues, by generating viable homozygous Rpl3l knockout mouse strain. We identify rescue mechanism which, upon depletion, becomes...
The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions experimental validation...
Abstract The human transcriptome contains thousands of small open reading frames (sORFs) that encode microproteins whose functions remain largely unexplored. Here, we show TINCR lncRNA encodes pTINCR, an evolutionary conserved ubiquitin-like protein (UBL) expressed in many epithelia and upregulated upon differentiation under cellular stress. By gain- loss-of-function studies, demonstrate pTINCR is a key inducer epithelial vitro vivo. Interestingly, low expression associates with worse...
A major scientific drive is to characterize the protein-coding genome as it provides primary basis for study of human health. But fundamental question remains: what has been missed in prior genomic analyses? Over past decade, translation non-canonical open reading frames (ncORFs) observed across cell types and disease states, with implications proteomics, genomics, clinical science. However, impact ncORFs limited by absence a large-scale understanding their contribution proteome. Here, we...
Abstract The birth of genes that encode new protein sequences is a major source evolutionary innovation. However, we still understand relatively little about how these come into being and which functions they are selected for. To address questions, have obtained large collection mammalian-specific gene families lack homologues in other eukaryotic groups. We combined annotations de novo transcript assemblies from 30 different mammalian species, obtaining ∼6,000 families. In general, the...
The differential production of transcript isoforms from gene loci is a key cellular mechanism. Yet, its impact in protein remains an open question. Here, we describe ORQAS (ORF quantification pipeline for alternative splicing), the translation individual using ribosome-protected mRNA fragments (ribosome profiling). We find evidence 40-50% expressed human and mouse, with 53% genes having more than one translated isoform human, 33% mouse. Differential splicing analysis revealed that about 40%...
Evolutionary innovations can be driven by changes in the rates of RNA translation and emergence new genes small open reading frames (sORFs). In this study, we characterized transcriptional translational landscape hearts four primate two rodent species through integrative ribosome transcriptomic profiling, including adult left ventricle tissues induced pluripotent stem cell-derived cardiomyocyte cell cultures. We show here that efficiencies subunits mitochondrial oxidative phosphorylation...
Abstract Thousands of short open reading frames (sORFs) are translated outside annotated coding sequences. Recent studies have pioneered searching for sORF-encoded microproteins in mass spectrometry (MS)-based proteomics and peptidomics datasets. Here, we assessed literature-reported MS-based identifications unannotated human proteins. We find that vary by three orders magnitude the number proteins they report. Of nearly 10,000 reported peptides, 96% were unique to a single study, 12% mapped...
Long non-coding RNAs (lncRNAs) are well-established as key regulators of gene expression. However, emerging evidence reveals that some lncRNAs can also encode functional microproteins. In this study, we report the identification an evolutionarily young microprotein encoded by LINC01503 , expressed across several human tissues. This microprotein, designated LINC01503-MP, localises to mitochondria and exerts a proliferative effect on HCT116 colorectal cancer (CRC) cells. Functional studies...
Abstract The mammalian transcriptome includes thousands of transcripts that do not correspond to annotated protein-coding genes and are known as long non-coding RNAs (lncRNAs). A handful lncRNAs have well-characterized regulatory functions but the biological significance majority them is well understood. LncRNAs conserved between mice humans likely be enriched in functional sequences. Here, we investigate presence different types ribosome profiling signatures how they relate sequence...