A5072633078- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Viral Infections and Immunology Research
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Molecular Biology Techniques and Applications
- Retinal Development and Disorders
- Chronic Lymphocytic Leukemia Research
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- ATP Synthase and ATPases Research
- CRISPR and Genetic Engineering
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Blood disorders and treatments
- Cellular Mechanics and Interactions
- Photochromic and Fluorescence Chemistry
- Click Chemistry and Applications
- T-cell and Retrovirus Studies
- Advanced biosensing and bioanalysis techniques
- Cancer Mechanisms and Therapy
- Genetic and Kidney Cyst Diseases
- Photoreceptor and optogenetics research
Centre for Genomic Regulation
2012-2024
Institute of Science and Technology
2024
Barcelona Institute for Science and Technology
2023-2024
Universitat Pompeu Fabra
2008-2023
Inserm
2001-2007
Université Toulouse III - Paul Sabatier
2007
Institut Claudius Regaud
2007
The University of Texas MD Anderson Cancer Center
2001
The Polycomb repressive complex 2 (PRC2) mediates epigenetic maintenance of gene silencing in eukaryotes via methylation histone H3 at lysine 27 (H3K27). Accessory factors define two distinct subtypes, PRC2.1 and PRC2.2, with different actions chromatin-targeting mechanisms. mechanisms orchestrating PRC2 assembly are not fully understood. Here, we report that alternative splicing (AS) core component SUZ12 generates an uncharacterized isoform SUZ12-S, which co-exists the canonical SUZ12-L...
The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report transcriptome-wide analyses upon systematic knock down of 305 components and regulators human cancer cells reconstruction functional splicing factor networks govern different classes alternative decisions. results disentangle intricate circuits...
The 484-nucleotide (nt) alternatively translated region (ATR) of the human fibroblast growth factor 2 (FGF-2) mRNA contains four CUG and one AUG translation initiation codons. Although 5′-end proximal codon is initiated by a cap-dependent process, other codons are mechanism internal entry ribosomes. We undertook here detailed analysis cis-acting elements defining FGF-2 ribosome site (IRES). A thorough deletion study within 5′-ATR led us to define 176-nt as being necessary sufficient for IRES...
Alternative initiation of translation the human fibroblast growth factor 2 (FGF-2) mRNA at five in-frame CUG or AUG codons requires various RNA <i>cis</i>-acting elements, including an internal ribosome entry site (IRES). Here we describe purification a <i>trans</i>-acting controlling FGF-2 achieved by several biochemical approaches. We have identified heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as that binds to 5′-leader and also complements defective <i>in vitro</i> in rabbit...
Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a nucleocytoplasmic shuttling protein that regulates gene expression through its action on mRNA metabolism and translation. The cytoplasmic redistribution of hnRNP regulated process during viral infection cellular stress. Here, we show an internal ribosome entry site (IRES) trans-acting factor binds specifically to the 5' untranslated region both human rhinovirus-2 apoptotic peptidase activating 1 (apaf-1) mRNAs, thereby regulating their...
Translation of the X-linked inhibitor apoptosis (XIAP) proceeds by internal ribosome entry site (IRES)-mediated initiation, a process that is physiologically important because XIAP expression essential for cell survival under conditions compromised cap-dependent translation, such as cellular stress. The regulation initiation requires interaction IRES trans-acting factors (ITAFs) with element. We used RNA-affinity chromatography to identify ITAFs and isolated heterogeneous nuclear...
Transition from maternal to embryonic transcriptional control is crucial for embryogenesis. However, alternative splicing regulation during this process remains understudied. Using transcriptomic data human, mouse, and cow preimplantation development, we show that the stage of zygotic genome activation (ZGA) exhibits highest levels exon skipping diversity reported any cell or tissue type. Much temporary, leads disruptive noncanonical isoforms, occurs in genes enriched DNA damage response...
Alternative splicing increases neuronal transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling assembly and evolution of this regulatory layer, we characterized microexon program in Drosophila compared it with that mammals. In nonvertebrate bilaterians, is restricted to neurons by posttranscriptional processing enhancer microexons (eMIC) domain Srrm234 . , dependent on regulation Elav/Fne. eMIC deficiency or misexpression leads widespread neurological...
Retinal photoreceptors have a distinct transcriptomic profile compared to other neuronal subtypes, likely reflecting their unique cellular morphology and function in the detection of light stimuli by way ciliary outer segment. We discovered layer this molecular specialization revealing that vertebrate retina expresses largest number tissue-enriched microexons all tissue types. A subset these is included exclusively photoreceptor transcripts, particularly genes involved cilia biogenesis...
Abstract The RNA-binding motif protein RBM5 belongs to a family of multi-domain RNA binding proteins that regulate alternative splicing genes important for apoptosis and cell proliferation have been implicated in cancer. harbors structural modules recognition, such as RRM domains Zn finger, protein-protein interactions an OCRE domain. Here, we characterize the RRM1-ZnF1-RRM2 cis -regulatory elements. A structure RRM1-ZnF1 region complex with shows how tandem cooperate sandwich target...
Internal Ribosome Entry Sites (IRES) are cis-acting RNA sequences able to mediate internal entry of the 40S ribosomal subunit on some eukaryotic and viral messenger RNAs upstream a translation initiation codon. These very diverse present in growing list mRNAs. Novel IRES continue be added public databases every year unknown IRESes is certainly still large. The database comprehensive WWW resource for ribosome sites presents currently available general information as well detailed data each...
The multi-domain splicing factor RBM5 regulates the balance between antagonistic isoforms of apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE (OCtamer REpeat aromatic residues) domain found in is important for alternative regulation mediates interactions with components U4/U6.U5 tri-snRNP. We show that adopts a unique β–sheet fold. NMR biochemical experiments demonstrate directly binds to proline-rich C-terminal tail essential snRNP core proteins SmN/B/B’. structure an OCRE-SmN...
Alternative splicing is crucial for cancer progression and can be targeted pharmacologically, yet identifying driver exons genome-wide remains challenging. We propose such by associating statistically gene-level dependencies from knockdown viability screens with profiles gene expression. Our models predict the effects of perturbations on cell proliferation transcriptomic data, enabling in silico RNA screening prioritizing targets splicing-based therapies. identified 1,073 impacting...
Spinal Muscular atrophy is a prevalent genetic disease caused by mutation of the SMN1 gene, which encodes SMN protein involved in assembly small nuclear ribonucleoprotein (snRNP) complexes. A paralog SMN2 , cannot provide adequate levels functional because exon 7 skipped significant fraction mature transcripts. C to T transition located at position 6 critical for difference skipping between and . Here we report that this nucleotide results increased ultraviolet light-mediated crosslinking...
Splicing factor 3B subunit 1 (SF3B1) is involved in pre-mRNA branch site recognition and the target of antitumor-splicing inhibitors. Mutations SF3B1 are observed 15% patients with chronic lymphocytic leukemia (CLL) associated poor prognosis, but their pathogenic mechanisms remain poorly understood. Using deep RNA-sequencing data from 298 CLL tumor samples isogenic WT K700E-mutated cell lines, we characterize targets sequence features selection cryptic 3′ splice sites upon mutation,...
Resistance to MAPK inhibitors (MAPKi), the main cause of relapse in BRAF-mutant melanoma, is associated with production alternative BRAF mRNA isoforms (altBRAFs) up 30% patients receiving inhibitor monotherapy. These altBRAFs have been described as being generated by pre-mRNA splicing, and splicing modulation has proposed a therapeutic strategy overcome resistance. In contrast, we report that are through genomic deletions. Using different vitro models altBRAF-mediated melanoma resistance,...