A5027911405- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Polyamine Metabolism and Applications
- RNA Interference and Gene Delivery
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- Cannabis and Cannabinoid Research
- Pancreatic function and diabetes
- Cancer-related molecular mechanisms research
- Neuroscience of respiration and sleep
- Protein Degradation and Inhibitors
- Genomics and Phylogenetic Studies
- Insect Resistance and Genetics
European Molecular Biology Laboratory
2021-2024
Cancer Research UK
2018-2021
University of Cambridge
2018-2021
Cancer Research UK Cambridge Center
2019-2021
Boston Children's Hospital
2016-2019
Abstract Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here we develop a modular epigenome editing platform that programs nine key chromatin modifications, or combinations thereof, to precise loci in living cells. We couple this single-cell readouts systematically quantitate the magnitude heterogeneity transcriptional responses elicited by each specific modification....
The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila, piRNA-guided silencing achieved, part, via co-transcriptional repression by Piwi. This depends on Panoramix (Panx); however, precisely how an binding event silences transcription remains to be determined. Here we show Nuclear Export Factor 2 (Nxf2) its co-factor, Nxt1, form complex with Panx are required for...
Mutations in the 3'-5' exonuclease DIS3L2 are associated with Perlman syndrome and hypersusceptibility to Wilms tumorigenesis. Previously, we found that Dis3l2 specifically recognizes degrades uridylated pre-let-7 microRNA. However, widespread relevance of Dis3l2-mediated decay substrates remains unknown. Here, applied an unbiased RNA immunoprecipitation strategy identify targets mouse embryonic stem cells. The disease-associated long noncoding (lncRNA) Rmrp, 7SL, as well several other Pol...
The PIWI-interacting RNA (piRNA) pathway is a conserved small RNA-based immune system that protects animal germ cell genomes from the harmful effects of transposon mobilization. In Drosophila ovaries, most piRNAs originate dual-strand clusters, which generate both genomic strands. Dual-strand clusters use noncanonical transcription mechanisms. Although transcribed by polymerase II, cluster transcripts lack splicing signatures and poly(A) tails. mRNA processing important for general export...
The Piwi-interacting RNA (piRNA) pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires specialized machinery converts long single-stranded precursors into RNAs of ∼25-nucleotides length. This process involves factors operate two different subcellular compartments: the nuage/Yb body and mitochondria. How these sites communicate to achieve accurate substrate selection efficient processing remains unclear. Here, we...
In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through co-transcriptional gene silencing of transposon insertions.
The nuclear pore complex (NPC) is the principal gateway between nucleus and cytoplasm that enables exchange of macromolecular cargo. Composed multiple copies ~30 different nucleoporins (Nups), NPC acts as a selective portal, interacting with factors which individually license passage specific cargo classes. Here we show two Nups inner channel, Nup54 Nup58, are essential for transposon silencing via PIWI-interacting RNA (piRNA) pathway in Drosophila ovary. In ovarian follicle cells, loss...
ABSTRACT Chromatin modifications are linked with regulating patterns of gene expression, but their causal role and context-dependent impact on transcription remains unresolved. Here, we develop a modular epigenome editing platform that programmes nine key chromatin – or combinations thereof to precise loci in living cells. We couple this single-cell readouts systematically quantitate the magnitude heterogeneity transcriptional responses elicited by each specific modification. Amongst these,...
Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether dystrophic phenotype also linked CNBP decrease, a conserved CCHC-type zinc finger RNA-binding that regulates translation required for mammalian development. Here, we show depletion Drosophila muscles causes ageing-dependent locomotor defects are correlated impaired...
Abstract The piRNA pathway is a conserved, small RNA-based immune system that protects animal germ cell genomes from the harmful effects of transposon mobilisation. In Drosophila ovaries, most piRNAs originate dual-strand clusters, which generate both genomic strands. Dual-strand clusters use non-canonical transcription mechanisms. Although transcribed by RNA polymerase II, cluster transcripts lack splicing signatures and poly(A) tails. mRNA processing important for general export mediated...
ABSTRACT The piRNA pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. biogenesis requires specialised machinery converts long single-stranded precursors into RNAs of ~25-nucleotides length. This process involves factors operate two different subcellular compartments: the nuage/Yb-body and mitochondria. How these sites communicate to achieve accurate substrate selection efficient processing remains unclear. Here, we investigate previously...
Summary The PIWI-interacting RNA (piRNA) pathway is a small RNA-based immune system that controls the expression of transposons and maintains genome integrity in animal gonads. In Drosophila , piRNA-guided silencing achieved, part, via co-transcriptional repression by Piwi. This depends on Panoramix (Panx); however, precisely how an binding event silences transcription remains to be determined. Here we show Nuclear Export Factor 2 (Nxf2) its cofactor, Nxt1, form complex with Panx are...
ABSTRACT Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation toxic RNA and have been associated DM2. However, it is still unclear whether dystrophic phenotype also linked decrease, a conserved CCHC-type zinc finger binding protein that regulates translation required for mammalian development. Here we show depletion Drosophila muscles causes age-dependent locomotor defects are correlated with impaired polyamine metabolism. We demonstrate levels ornithine...
Abstract In animal gonads, the PIWI-interacting RNA (piRNA) pathway guards genome integrity in part through co-transcriptional gene silencing of transposon insertions. Drosophila ovaries, piRNA-loaded Piwi detects nascent transcripts and instructs heterochromatin formation P anoramix- i nduced c o- t ranscriptional s ilencing (PICTS) complex, containing Panoramix, Nxf2 Nxt1. Here, we report that highly conserved dynein light chain LC8/Cut-up (Ctp) is an essential component PICTS complex....