A5041569034- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- RNA Interference and Gene Delivery
- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- interferon and immune responses
- Chromosomal and Genetic Variations
- DNA and Nucleic Acid Chemistry
- Malaria Research and Control
- Genomics and Chromatin Dynamics
- Advanced MRI Techniques and Applications
- Trypanosoma species research and implications
- Epigenetics and DNA Methylation
- Chemical Synthesis and Analysis
- Advanced biosensing and bioanalysis techniques
- Redox biology and oxidative stress
- Sulfur Compounds in Biology
University College London
2014-2024
Institute of Structural and Molecular Biology
2014-2024
The Francis Crick Institute
2007-2017
Birkbeck, University of London
2016
Lehigh University
2015
University of Alberta
2015
University of Cambridge
2015
University of Hong Kong
2015
MRC London Institute of Medical Sciences
2015
Medical Research Council
2010-2014
NMR titration experiments are a rich source of structural, mechanistic, thermodynamic and kinetic information on biomolecular interactions, which can be extracted through the quantitative analysis resonance lineshapes. However, applications such analyses frequently limited by peak overlap inherent to complex systems. Moreover, systematic errors may arise due two-dimensional data using theoretical frameworks developed for one-dimensional experiments. Here we introduce more accurate convenient...
In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how KH modules participate recognition targets is necessary to dissect way these operate. We have designed mutant with impaired capability for general use exploring individual combinatorial functional targets. A double mutation hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without...
Significance Long noncoding RNAs (lncRNAs) provide new layers of complexity to gene expression control. We report on the functional consequences interaction between ssRNA-binding protein K homology-type splicing regulatory (KSRP) with H19 lncRNA (H19) in multipotent C2C12 cells able differentiate culture toward myotubes response activation cell signaling pathways, including AKT. KSRP and interact exclusively undifferentiated cells, this favors KSRP’s ability promyogenic transcript myogenin...
Exosomal miRNA transfer is a mechanism for cell-cell communication that important in the immune response, functioning of nervous system and cancer. Syncrip/hnRNPQ highly conserved RNA-binding protein mediates exosomal partition set miRNAs. Here, we report Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, cryptic, sequence-specific designated NURR (N-terminal unit RNA recognition). The domain specific recognition short hEXO sequence...
Cyclic AMP (cAMP) is an important signalling molecule across evolution, but its role in malaria parasites poorly understood. We have investigated the of cAMP asexual blood stage development Plasmodium falciparum through conditional disruption adenylyl cyclase beta (ACβ) and downstream effector, cAMP-dependent protein kinase (PKA). show that both production activity PKA are critical for erythrocyte invasion, whilst key developmental steps precede invasion still take place absence signalling....
Tudor domains are found in many organisms and have been implicated protein-protein interactions which methylated protein substrates bind to these domains. Here, we present evidence for the involvement of specific germline development. Drosophila Tudor, founder domain family, contains 11 is a component polar granules nuage, electron-dense organelles characteristic organisms, including mammals. In this study, investigated whether fulfil functions granule assembly, germ cell formation abdomen...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA New Method To Detect Long-Range Protein−RNA Contacts: NMR Detection of Electron−Proton Relaxation Induced by Nitroxide Spin-Labeled RNAAndres Ramos and Gabriele VaraniView Author Information MRC Laboratory Molecular Biology Hills Road, Cambridge CB2 2QH, England Cite this: J. Am. Chem. Soc. 1998, 120, 42, 10992–10993Publication Date (Web):October 7, 1998Publication History Received15 July 1998Revised10 September 1998Published online7...
MicroRNAs (miRNAs) interact with 3′-untranslated regions of messenger RNAs to restrict expression most protein-coding genes during normal development and cancer. RNA-binding proteins (RBPs) can control the biogenesis, stability activity miRNAs. Here we identify RBM38 in a genetic screen for RBPs whose controls miRNA access target mRNAs. is induced by p53 its ability modulate miRNA-mediated repression required proper function. In contrast, shows lower propensity block action p53-controlled...
Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers associated with upregulation key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, synergizes mutations Kras to enhance signalling oncogenic activity, suggesting that molecules inhibiting could have therapeutic potential. Here, we isolate a small molecule interacts hydrophobic surface at the boundary KH3 KH4 domains, inhibits RNA. In cells, compound reduces level other mRNA targets,...
Abstract Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates TH1 lineage, whereas GATA3 drives alternative TH2 However, LD-TFs, including and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing separately or together in mouse we show that sequesters at its target sites, thereby removing from genes. This redistribution independent DNA binding...
Fragile-X syndrome, the most common monogenic form of mental retardation, is caused by down-regulation expression Fragile X Mental Retardation Protein (FMRP). FMRP a multifunctional, multidomain RNA-binding protein that acts as translational repressor in neuronal cells. Interaction between and mRNA targets involves an RGG box, motif commonly thought to mediate unspecific interactions with nucleic acids. Instead, box has been shown recognize RNA G-quartet structures specifically be necessary...
Zipcode binding protein 1 (ZBP1) is an oncofetal RNA-binding that mediates the transport and local translation of β-actin mRNA by KH3-KH4 di-domain, which essential for neuronal development. The high-resolution structures with their respective target sequences show KH4 recognizes a non-canonical GGA sequence via enlarged dynamic hydrophobic groove, whereas KH3 to core CA occurs low specificity. A data-informed kinetic simulation two-step reaction reveals overall driven second event moderate...
Epitranscriptomics represents a further layer of gene expression regulation. Specifically, N6-methyladenosine (m6A) regulates RNA maturation, stability, degradation, and translation. Regarding microRNAs (miRNAs), while it has been reported that m6A impacts their biogenesis, the functional effects on mature miRNAs remain unclear. Here, we show modification specific weakens coupling to AGO2, impairs function target mRNAs, determines delivery into extracellular vesicles (EVs), provides...
The fidelity of translation the genetic code depends on accurate tRNA aminoacylation by cognate aminoacyl-tRNA synthetases. Thus, each has specificity not only for codon recognition, but also amino acid identity; this is referred to as identity. primary determinant acceptor identity Escherichia coli tRNAAla a wobble G3·U70 pair within stem. Despite extensive biochemical and data, mechanism which marks end with alanine been clarified at molecular level. solution structure microhelix derived...
Fragile X syndrome, the most common cause of inherited mental retardation, is caused by absence fragile retardation protein (FMRP). The emerging picture that FMRP involved in repression translation through a complex network protein−protein and protein−RNA interactions. Very little structural information is, however, available for could help to understand its function. In particular, no studies are about N-terminus protein, highly conserved region which several molecular Here, we explore...