- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Neurogenetic and Muscular Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- Cancer-related molecular mechanisms research
- HVDC Systems and Fault Protection
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Cancer-related gene regulation
The Francis Crick Institute
2021-2023
Centre for Genomic Regulation
2019-2022
Universitat Pompeu Fabra
2020-2022
Barcelona Institute for Science and Technology
2019
Istituti di Ricovero e Cura a Carattere Scientifico
2018
N6-methyladenosine (m6A) is a widely studied and abundant RNA modification. The m6A mark regulates the fate of RNAs in various ways, which turn drives changes cell physiology, development, disease pathology. Over last decade, numerous methods have been developed to map quantify sites genome-wide through deep sequencing. Alternatively, levels can be quantified from population using techniques such as liquid chromatography-mass spectrometry or thin layer chromatography. However, many for...
Most genes are transcribed from multiple transcription start sites (TSSs), defined as alternative TSSs, which highly regulated and can lead to various gene regulatory outcomes including changes in translation efficiency protein isoform expression. Transcription factors chromatin regulators control TSS selection. DNA supercoiling affects aspects of initiation; however, its effect on with TSSs is not known. Here, we investigated how impacts usage Saccharomyces cerevisiae. We depleted...
Transcription initiation is a highly dynamic and tightly regulated process involving the coordinated action of transcription factors, chromatin remodelers, RNA polymerase which determine where when begins. Accurately mapping quantifying start sites (TSSs) from nascently transcribed RNAs remains key area interest, as it provides critical insights into dynamics. Here, we combined transient transcriptome sequencing with site (TT-TSS-seq) to accurately map quantify nascent transcripts. Since...
The regulation of pre-mRNA processing has important consequences for cell division and the control cancer proliferation, but underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, CHERP, form a tight physical functionally coherent complex regulates variety alternative events, frequently by repressing short exons flanked suboptimal 3′ splice sites. These comprise embedded in genes with functions cell-cycle progression, including G2/M key...
Abstract Background Somatic cell reprogramming is the process that allows differentiated cells to revert a pluripotent state. In contrast extensively studied rewiring of epigenetic and transcriptional programs required for reprogramming, dynamics post-transcriptional changes their associated regulatory mechanisms remain poorly understood. Here we study alternative splicing occurring during efficient mouse B into induced stem (iPS) compare them those embryonic fibroblasts. Results We observe...
Alternative splicing is a prevalent mechanism of gene regulation that modulated in response to wide range extracellular stimuli. Stress-activated protein kinases (SAPKs) play key role controlling several steps mRNA biogenesis. Here, we show osmostress has an impact on the alternative (AS), which partly mediated through action p38 SAPK. Splicing network analysis revealed functional connection between and spliceosome component SKIIP, whose depletion abolished significant fraction p38-mediated...
Abstract Mutations in RNA-binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb, and neurological symptoms. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved nucleic acid binding, transcription, splicing through direct binding DNA RNA, or interaction with other the spliceosome. We show a developmental role for Hnrnpul1 zebrafish, resulting reduced body fin growth missing bones. Defects craniofacial tendon adult-onset caudal scoliosis also...
The directionality of gene promoters-the ratio protein-coding over divergent noncoding transcription-is highly variable. How promoter is controlled remains poorly understood. Here, we show that the chromatin remodelling complex RSC and general regulatory factors (GRFs) dictate by attenuating transcription relative to transcription. At promoters are directional, depletion leads a increase in thus decrease directionality. We find has modest effect on nucleosome positioning upstream at sites...
Abstract Mutations in RNA binding proteins can lead to pleiotropic phenotypes including craniofacial, skeletal, limb and neurological symptoms. Heterogeneous Nuclear Ribonucleoproteins (hnRNPs) are involved nucleic acid binding, transcription splicing through direct DNA RNA, or interaction with other the spliceosome. We show a developmental role for Hnrnpul1 zebrafish, resulting reduced craniofacial tendon length, severe adult-onset scoliosis fin size. demonstrate of alternative...
The directionality of gene promoters - the ratio protein-coding over divergent noncoding transcription is highly variable and regulated. How promoter controlled remains poorly understood. Here, we show that chromatin remodelling complex RSC general regulatory factors (GRFs) dictate by attenuating transcription. At are directional, depletion leads to a relative increase in thus decrease directionality. We find facilitates nucleosome positioning upstream at sites These directional also...
Abstract In contrast to the extensively studied rewiring of epigenetic and transcriptional programs required for cell reprogramming, dynamics post-transcriptional changes their associated regulatory mechanisms remain poorly understood. Here we have alternative splicing (AS) occurring during efficient reprogramming mouse B cells into induced pluripotent stem (iPS) cells. These changes, generally uncoupled from regulation, significantly overlapped with reported embryonic fibroblasts (MEFs)....