A5043498560- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Bacterial Genetics and Biotechnology
- Nuclear Structure and Function
- Herpesvirus Infections and Treatments
- RNA regulation and disease
- Developmental Biology and Gene Regulation
- MicroRNA in disease regulation
- Viral-associated cancers and disorders
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- Animal Genetics and Reproduction
- Genomics and Phylogenetic Studies
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Neurogenetic and Muscular Disorders Research
- HVDC Systems and Fault Protection
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Genomics and Chromatin Dynamics
- Protein Structure and Dynamics
- Amyotrophic Lateral Sclerosis Research
- Axon Guidance and Neuronal Signaling
- Congenital heart defects research
University of Sheffield
2012-2025
Newcastle University
2023-2024
University of Pennsylvania
2023-2024
University of Manchester
1986-2010
University of Oxford
1998-2001
University of Sussex
1998-1999
University College London
1991-1997
The Royal Free Hospital
1997
John Radcliffe Hospital
1996
Increasing a protein concentration in solution to the required level, without causing aggregation and precipitation is often challenging but important task, especially field of structural biology; as little 20% nonmembrane proteins have been found be suitable candidates for studies predominantly due poor solubility. We demonstrate here that simultaneous addition charged amino acids l-Arg l-Glu at 50 mM buffer can dramatically increase maximum achievable soluble (up 8.7 times). These are...
GGGGCC repeat expansions of C9orf72 represent the most common genetic variant amyotrophic lateral sclerosis and frontotemporal degeneration, but mechanism pathogenesis is unclear. Recent reports have suggested that transcribed might form toxic RNA foci sequester various processing proteins. Consensus as to identity binding partners missing whole neuronal proteome investigation needed. Using fluorescence in situ hybridization we first identified nuclear cytoplasmic peripheral central nervous...
Abstract Despite the nuclear localization of m 6 A machinery, genomes multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively A-modified. However, these findings mostly based on A-Seq, an antibody-dependent technique with a high rate false positives. Here, we address presence in CHIKV DENV RNAs. For this, combine A-Seq antibody-independent SELECT nanopore direct sequencing techniques functional, molecular, mutagenesis...
The conserved TREX mRNA export complex is known to contain UAP56, Aly, Tex1, and the THO complex. Here, we carried out proteomic analysis of immunopurified human identified protein CIP29 as only new component with a clear yeast relative (known Tho1). Tho1 function in export, provide evidence that likewise functions this process. Like components, portion localizes nuclear speckle domains, its efficient recruitment both splicing- cap-dependent. We show UAP56 mediates an ATP-dependent...
Adaptor proteins stimulate the nuclear export of mRNA, but their mechanism action remains unclear. Here, we show that REF/ALY binds mRNA; upon formation a ternary complex with TAP RNA is transferred from REF to TAP, and overexpression displaces mRNA in vivo. also handed over two other adaptors, 9G8 SRp20 complex. Interestingly, RNA-binding affinity enhanced 4-fold vitro once it complexed REF. enhance activity vitro. Consistent model which directly adaptors during export, vivo by an...
Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from nucleus to cytoplasm. They couple early processing events such as 5' capping and 3' end formation with loading TAP/NXF1 receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited via UAP56 subsequently delivers NXF1 [1]. Knockdown [2, 3] [4-7] higher eukaryotes efficiently blocks export, whereas knockdown REF only causes a modest reduction, suggesting existence additional [8-10]. Here we...
N6-methyladenosine (m6A) is the most abundant internal RNA modification of cellular mRNAs. m6A recognised by YTH domain-containing proteins, which selectively bind to m6A-decorated RNAs regulating their turnover and translation. Using an m6A-modified hairpin present in Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from ‘Royal family’ as putative readers, including SND1. RIP-seq eCLIP analysis characterised SND1 binding profile transcriptome-wide,...
The structure of BPSL1549, a protein unknown function from Burkholderia pseudomallei, reveals similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as potent cytotoxin against eukaryotic cells and was lethal when administered mice. Expression levels bpsl1549 correlate with conditions expected promote or suppress pathogenicity. promotes deamidation glutamine-339 the translation initiation eIF4A, abolishing its helicase activity inhibiting translation. propose name
N6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This has previously been shown to alter export kinetics for mRNAs though molecular details surrounding this phenomenon remain poorly understood. Recruitment TREX mRNA complex driven by transcription, 5' capping and pre-mRNA splicing. Here we identify a fourth mechanism in human cells driving association with involving m6A methylase complex. We show that recruits modified process essential their efficient...
During gene expression, RNA export factors are mainly known for driving nucleo-cytoplasmic transport. While early studies suggested that the exon junction complex (EJC) provides a binding platform them, subsequent work proposed they only recruited by cap to 5' end of RNAs, as part TREX. Using iCLIP, we show receptor Nxf1 and two TREX subunits, Alyref Chtop, whole mRNA co-transcriptionally via splicing but before 3' processing. Consequently, alters decisions Chtop regulates alternative...
The binding of extracellular ATP to the P2X7 receptor opens an integral cation-permeable channel; it also leads membrane blebbing and, in certain immune cells, interleukin-1β secretion and eventual death. latter three effects are unique receptor; among P2X receptors is long intracellular C terminus protein. We have shown that C-terminal domain P2X7receptor responsible for cell phenotype. A screen proteins associate with might mediate phenotype, identified epithelial protein 2 (EMP-2)....
Spatial organisation of nuclear compartments is an important regulator chromatin function, yet the molecular principles that maintain architecture remain ill-defined. We have used RNA interference to deplete key structural proteins, lamins. In HeLa cells, we show reduced expression lamin B1, but not A/C, severely inhibits synthesis – first by polymerase II and later I. Declining levels transcription correlate with different morphological changes in major compartments, nucleoli speckles....
Cancer testis antigens (CTAs) represented a poorly characterized group of proteins whose expression is normally restricted to but are frequently up-regulated in cancer cells. Here we show that one CTA, Luzp4, an mRNA export adaptor. It associates with the TREX complex subunit Uap56 and harbours binding motif, conserved other adaptors. Luzp4 binds principal receptor Nxf1, enhances its RNA activity complements Alyref knockdown vivo. Whilst range tumours, it appears preferentially expressed...