- Protein Kinase Regulation and GTPase Signaling
- Plant Molecular Biology Research
- Plant and Fungal Interactions Research
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Cellular Mechanics and Interactions
- Chromosomal and Genetic Variations
- Cancer-related molecular mechanisms research
- Microtubule and mitosis dynamics
- Metabolism, Diabetes, and Cancer
- Photosynthetic Processes and Mechanisms
- Plant Disease Resistance and Genetics
- Peptidase Inhibition and Analysis
- Cellular transport and secretion
- Microbial Metabolic Engineering and Bioproduction
- Pregnancy and preeclampsia studies
- Cancer-related Molecular Pathways
- Melanoma and MAPK Pathways
- Viral Infectious Diseases and Gene Expression in Insects
- Plant Pathogens and Fungal Diseases
- Ubiquitin and proteasome pathways
- Erythrocyte Function and Pathophysiology
- Birth, Development, and Health
- Hippo pathway signaling and YAP/TAZ
Novo Nordisk (Denmark)
2024
University of British Columbia
2022
University of Ottawa
2012-2021
University of Copenhagen
2017-2020
Wellcome Centre for Cell Biology
2014-2019
University of Edinburgh
2014-2019
Planta
2019
University of Windsor
2008
Abstract Most DNA in the genomes of higher organisms does not encode proteins, yet much is transcribed by RNA polymerase II (RNAPII) into long non-coding RNAs (lncRNAs). The biological significance most lncRNAs largely unclear. Here, we identify a lncRNA ( SVALKA ) cold-sensitive region Arabidopsis genome. Mutations affect CBF1 expression and freezing tolerance. RNAPII read-through transcription results cryptic overlapping on antisense strand, termed asCBF1 . Our molecular dissection reveals...
Abstract Most long non-coding RNAs (lncRNAs) encoded by eukaryotic genomes remain uncharacterized. Here we focus on a set of intergenic lncRNAs in fission yeast. Deleting one these exhibited clear phenotype: drug sensitivity. Detailed analyses the affected locus revealed that transcription nc-tgp1 lncRNA regulates tolerance repressing adjacent phosphate-responsive permease gene transporter for glycerophosphodiester 1 ( tgp1 + ). We demonstrate act transcribing over promoter increases...
Progression of RNA polymerase II (RNAPII) transcription relies on the appropriately positioned activities elongation factors. The resulting profile factors and chromatin signatures along units provides a "positional information system" for transcribing RNAPII. Here, we investigate chromatin-based mechanism that suppresses intragenic initiation RNAPII transcription. We demonstrate across gene promoters represses their function in plants. This repression is characterized by reduced...
Abstract RNA polymerase II (RNAPII) transcription converts the DNA sequence of a single gene into multiple transcript isoforms that may carry alternative functions. Gene result from variable start sites (TSSs) at beginning and polyadenylation (PASs) end transcripts. How TSSs relate to PASs is poorly understood. Here, we identify both ends molecules in Arabidopsis thaliana by isoform sequencing (TIF-seq) report four per expressed gene. While intragenic initiation represents large source...
Abstract Despite the conserved essential function of centromeres, centromeric DNA itself is not conserved. The histone-H3 variant, CENP-A, epigenetic mark that specifies centromere identity. Paradoxically, CENP-A normally assembles on particular sequences at specific genomic locations. To gain insight into specification complex here we take an evolutionary approach, fully assembling genomes and centromeres related fission yeasts. Centromere domain organization, but sequence, between...
Long non-coding RNA (lncRNA) transcription into a downstream promoter frequently results in transcriptional interference. However, the mechanism of this repression is not fully understood. We recently showed that drug tolerance fission yeast Schizosaccharomyces pombe controlled by lncRNA upstream tgp1+ permease gene. Here we demonstrate interference involves several transcription-coupled chromatin changes mediated conserved elongation factors Set2, Clr6CII, Spt6 and FACT. These are known to...
Abstract Background Unraveling the signaling pathways responsible for establishment of a metastatic phenotype in carcinoma cells is critically important understanding pathology cancer. The acquisition cell motility key property tumor and prerequisite invasion. Rho GTPases regulate actin cytoskeleton reorganization cellular responses required Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates activity Rac1 RhoA. DGKζ mRNA highly...
Rho GTPases share a common inhibitor, guanine nucleotide dissociation inhibitor (RhoGDI), which regulates their expression levels, membrane localization, and activation state. The selective of individual from RhoGDI ensures appropriate responses to cellular signals, but the underlying mechanisms are unclear. Diacylglycerol kinase ζ (DGKζ), phosphorylates diacylglycerol yield phosphatidic acid, selectively dissociates Rac1 by stimulating PAK1-mediated phosphorylation on Ser-101/174....
Spy1A is a cyclin-like protein required for progression through the G(1)/S phase of cell cycle. Elevated levels have been implicated in tumorigenesis and are attributed to overriding DNA damage response enhancing proliferation. Understanding how produced degraded essential resolving it contributes normal abnormal growth processes. Herein, we demonstrate that cycle-dependent manner during mitosis via ubiquitin-proteasome system. We resolved E3 ligase phosphorylation sites mediating...
Macropinosomes arise from the closure of plasma membrane ruffles to bring about non-selective uptake nutrients and solutes into cells. The morphological changes underlying ruffle formation macropinosome biogenesis are driven by actin cytoskeleton rearrangements under control Rho GTPase Rac1. We showed previously that Rac1 is activated diacylglycerol kinase ζ (DGKζ), which phosphorylates yield phosphatidic acid. Here, we show DGKζ required for optimal macropinocytosis induced growth factor...
Cells can switch between Rac1 (lamellipodia-based) and RhoA (blebbing-based) migration modes, but the molecular mechanisms regulating this shift are not fully understood. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, forms independent complexes with RhoA, selectively dissociating each from their common inhibitor RhoGDI. DGKζ catalytic activity is required for dissociation dispensable dissociation; instead, stimulates release via a...
Abstract Disclosure: T. Garner: Grant Recipient; Self; Novo Nordisk. P. Murray: M. Hojby: Employee; Stock Owner; R. Ard: P.E. Clayton: A. Stevens: Background: Predicting GH therapy response from gene expression has the potential to improve clinical management of short stature. Treatment in children born small for gestational age (SGA) requires daily injections. Although no long-acting GHs (LAGHs) are currently approved SGA, results REAL5 (randomised, multinational, open-label, controlled,...
Despite the conserved essential function of centromeres, centromeric DNA itself is not 1–4 . The histone-H3 variant, CENP-A, epigenetic mark that specifies centromere identity 5–8 Paradoxically, CENP-A normally assembles on particular sequences at specific genomic locations. To gain insight into specification complex centromeres we took an evolutionary approach, fully assembling genomes and related fission yeasts. Centromere domain organization, but sequence, between Schizosaccharomyces...
Summary Most DNA in the genomes of higher organisms does not encode proteins, but is transcribed by RNA polymerase II (RNAPII) into long non-coding (lncRNA). The biological significance most lncRNA largely unclear. Here, we identify a ( SVALKA ) cold-sensitive region Arabidopsis genome. Mutations affect timing maximal CBF1 expression and freezing tolerance. RNAPII read-through transcription results cryptic overlapping on antisense strand, termed asCBF1 . anti-correlated with expression. Our...
SUMMARY Higher organisms achieve optimal gene expression by tightly regulating the transcriptional activity of RNA Polymerase II (RNAPII) along DNA sequences genes 1 . RNAPII density across genomes is typically highest where two key choices for transcription occur: near start sites (TSSs) and polyadenylation (PASs) at beginning end genes, respectively 2,3 Alternative TSSs PASs amplify number transcript isoforms from 4 , but how alternative connect to variable unresolved common...
Abstract Cells can switch between Rac1, lamellipodia-based and RhoA, blebbing-based migration modes but the molecular mechanisms regulating this choice are not fully understood. Diacylglycerol kinase ζ (DGKζ), which phosphorylates diacylglycerol to yield phosphatidic acid, forms independent complexes with Rac1 selectively dissociating each from RhoGDI. DGKζ catalytic activity is required for dissociation dispensable RhoA dissociation. Instead, functions as a scaffold that stimulates release...