- RNA Research and Splicing
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Nematode management and characterization studies
- RNA Interference and Gene Delivery
- Photosynthetic Processes and Mechanisms
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Parasite Biology and Host Interactions
- Retinoids in leukemia and cellular processes
- Insect and Arachnid Ecology and Behavior
- Advanced Electron Microscopy Techniques and Applications
- Forensic and Genetic Research
- Genetics and Neurodevelopmental Disorders
- Muscle Physiology and Disorders
- Parasites and Host Interactions
- Chromosomal and Genetic Variations
- Photochromic and Fluorescence Chemistry
- Protist diversity and phylogeny
University of Aberdeen
2013-2024
University of Birmingham
2022
The Honourable Society of Lincoln's Inn
1992-2003
Sanjay Gandhi Post Graduate Institute of Medical Sciences
2002
University of Bern
1997-2000
ETH Zurich
1990-1991
<h3>Background:</h3> Autism is a common childhood onset neurodevelopmental disorder, characterised by severe and sustained impairment of social interaction communication, as well notably restricted repertoire activities interests. Its aetiology multifactorial with strong genetic basis. EIF4E the rate limiting component eukaryotic translation initiation, plays key role in learning memory through its control within synapse. mediated final process modulated mammalian target rapamycin (mTOR),...
The SOS-inducible ruvA and ruvB gene products of Escherichia coli are required for normal levels genetic recombination DNA repair. In vitro, RuvA protein interacts specifically with Holliday junctions and, together RuvB (an ATPase), promotes their movement along DNA. This process, known as branch migration, is important the formation heteroduplex this paper, we show that proteins promote unwinding partially duplex Using single-stranded circular substrates annealed fragments (52-558...
Mutation in the UPF3B gene on chromosome X is implicated neurodevelopmental disorders including X-linked intellectual disability, autism and schizophrenia. The protein involved nonsense-mediated mRNA decay pathway (NMD) that controls stability functions prevention of synthesis truncated proteins. Here we show NMD components UPF1 are down-regulated during differentiation neural stem cells into neurons. Using tethered function assays found missense mutations described families with reduced...
The Escherichia coli RuvA and RuvB proteins mediate the branch migration of Holliday junctions in vitro. In presence stoichiometric amounts (1 dimer/12 nucleotides), can occur without need for RuvA. However, is required when concentration reduced 4-fold or more. Under optimal conditions, we found minimal protein requirement to be 1 dimer per 500-1100 nucleotides tetramer 600-1200 nucleotides. To determine roles migration, compared reactions mediated by only RuvB. time courses two were...
Histone proteins are essential for chromatin formation, and histone gene expression is coupled to DNA synthesis. In metazoans, the RNA binding protein HBP/SLBP involved in post-transcriptional control of expression. vitro assays have demonstrated that human mRNA 3′ end formation translation. We inhibited by interference determine its function during mitotic cell cycle. Inhibition resulted inhibition synthesis, cycle progression S phase proliferation. These findings indicate coordinate...
Metazoan replication-dependent histone mRNAs do not have a poly(A) tail but end instead in conserved stem–loop structure. Efficient translation of these is dependent on the binding protein (SLBP). Here we explore mechanism by which SLBP stimulates vertebrate cells, using tethered function assay and analyzing protein–protein interactions. We show for first time that translational stimulation increases during oocyte maturation at level initiation. demonstrate can interact directly with subunit...
As in all metazoans, the replication-dependent histone genes of Caenorhabditis elegans lack introns and contain a short hairpin structure 3′ untranslated region. This is key element for post-transcriptional regulation gene expression determines mRNA end formation, nuclear export, translation decay. All these steps contribute to S-phase-specific genes. The binding site hairpin-binding protein that required hairpin-dependent regulation. Here, we demonstrate C. transcribed dividing cells during...
Using recombination intermediates made by RecA protein, we have shown that the Escherichia coli RuvB protein can mediate branch migration of Holliday junctions in vitro. The reaction is dependent on presence > or = 10 mM Mg2+ and stoichiometric amounts RuvB. E. RuvA reduces requirement for also (Muller, B., Tsaneva, I. R., West, S. C. (1993) J. Biol. Chem. 268, 17179-17184). To determine roles two proteins during migration, investigated interaction with DNA absence RuvA, (i) gel retardation...
DNA and histone synthesis are coupled ongoing replication is required to maintain gene expression. Here, we expose S phase–arrested cells the kinase inhibitors caffeine LY294002. This uncouples from messenger RNA (mRNA) abundance, altering efficiency of stress–induced mRNA down-regulation. Interference with caffeine-sensitive checkpoint kinases ataxia telangiectasia Rad3 related (ATR)/ataxia mutated (ATM) does not affect down- regulation, which indicates that ATR/ATM alone cannot account for...
The trans-splicing of short spliced leader (SL) RNAs onto the 5' ends mRNAs occurs in a diverse range taxa. In nematodes, all species so far characterized utilize characteristic, conserved leader, SL1, as well variants that are employed resolution operons. Here we report identification basal nematode Trichinella spiralis, and show this does not possess canonical but rather has at least 15 distinct leaders, encoded by 19 SL RNA genes. individual leaders vary both size primary sequence,...
The organization of genes into operons, clusters that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in wide range eukaryotic groups, including multiple animal phyla. Operons present the class Chromadorea, one two main nematode classes, but their distribution other class, Enoplea, not known. We have surveyed genomes Trichinella spiralis, Trichuris muris, and Romanomermis culicivorax identified first putative operons members Enoplea. Consistent with mechanism RNA...
Histone protein synthesis is essential for cell proliferation and required the packaging of DNA into chromatin. In animals, histone proteins are provided by expression multicopy replication-dependent genes. mRNAs that processed a histone-specific mechanism to end after highly conserved RNA hairpin element, lack poly(A) tail. vertebrates Drosophila, their dependent on HBP/SLBP binds element. We showed previously these cis trans acting regulators gene in C. elegans. Here we report results an...
Histone RNA 3′ processing in vitro produces one or more 5′ cleavage products corresponding to the mature histone mRNA end, and a group of whose ends are mostly located several nucleotides downstream end. The formation these is coupled dependent on U7 snRNP heat-labile factor. These short therefore true general feature reaction. Identical also formed from model containing all spacer but no sequences mRNA. Again, this reaction both Unlike with full-length pre-mRNA, only fragments. In addition,...
Spliced leader (SL) trans-splicing is a critical element of gene expression in number eukaryotic groups. This process arguably best understood nematodes, where biochemical and molecular studies Caenorhabditis elegans Ascaris suum have identified key steps factors involved. Despite this, the precise details SL yet to be elucidated. In part, this because systematic identification molecules involved has not previously been possible due lack specific phenotype associated with defects process. We...
Cap methyltransferases (CMTrs) O methylate the 2′ position of ribose (cOMe) cap-adjacent nucleotides animal, protist, and viral mRNAs. Animals generally have two CMTrs, whereas trypanosomes three, many viruses encode one in their genome. In splice leader mRNAs trypanosomes, first four contain cOMe, but little is known about status cOMe animals. Here, we show that prominently present on with species- tissue-specific variations Caenorhabditis elegans , honeybees, zebrafish, mouse, human cell...