A5052492428- Cytomegalovirus and herpesvirus research
- Viral-associated cancers and disorders
- Herpesvirus Infections and Treatments
- RNA modifications and cancer
- Virus-based gene therapy research
- Polyomavirus and related diseases
- Cancer-related molecular mechanisms research
- Plant Virus Research Studies
- Parvovirus B19 Infection Studies
- RNA Research and Splicing
- Antenna Design and Analysis
- Full-Duplex Wireless Communications
- HVDC Systems and Fault Protection
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Bacteriophages and microbial interactions
- Circular RNAs in diseases
- Genetic factors in colorectal cancer
- RNA regulation and disease
- Transplantation: Methods and Outcomes
- interferon and immune responses
- RNA Interference and Gene Delivery
- Cardiac Structural Anomalies and Repair
- Animal Virus Infections Studies
- Cardiac Ischemia and Reperfusion
University of Leeds
2016-2025
Institute of Structural and Molecular Biology
2015-2024
Rhodes University
2018-2024
Institut de Biologie Moléculaire et Cellulaire
2005-2011
St James's University Hospital
1996-2002
University of Louisville
1992
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,...
Reactivation of lytic replication from viral latency is a defining property all herpesviruses. Despite this, the authentic physiological cues for latent-lytic switch are unclear. Such should ensure that occurs under conditions, predominantly in sites which facilitate transmission to permissive uninfected cells and new susceptible hosts. Kaposi's sarcoma-associated herpesvirus (KSHV) associated with B-cell neoplasm primary effusion lymphoma (PEL), virus remains latent. We have previously...
A cellular pre-mRNA undergoes various post-transcriptional processing events, including capping, splicing and polyadenylation prior to nuclear export. Splicing is particularly important for mRNA export as two distinct multi-protein complexes, known human TREX (hTREX) the exon-junction complex (EJC), are recruited in a splicing-dependent manner. In contrast, number of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic mRNAs lack introns exported by virus-encoded ORF57 protein. Herein we...
ABSTRACT The coronavirus nucleocapsid (N) protein plays a multifunctional role in the virus life cycle, from regulation of replication and transcription genome packaging to modulation host cell processes. These functions are likely be facilitated by interactions with proteins. potential interactome infectious bronchitis (IBV) N was mapped using stable isotope labeling amino acids culture (SILAC) coupled green fluorescent protein-nanotrap pulldown methodology liquid chromatography-tandem mass...
Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor cells. In 2008, novel human polyomavirus, polyomavirus (MCPyV), was identified and strongly implicated in MCC pathogenesis. Currently, little known regarding the virus-host interactions which support virus replication virus-induced mechanisms cellular transformation metastasis. Here we identify new function of MCPyV small T antigen (ST) as an inhibitor NF-κB-mediated...
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic associated with multiple AIDS-related malignancies. Like other herpesviruses, KSHV has a biphasic life cycle and both the lytic latent phases are required for tumorigenesis. Evidence suggests that replication can cause genome instability in KSHV-infected cells, although no mechanism thus far been described. A surprising link recently suggested between mRNA export, cancer development. Notably, aberrations cellular transcription...
ABSTRACT Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. polyomavirus (MCPyV) causes the majority MCC cases due to expression MCPyV small large tumor antigens (ST LT, respectively). Although number molecular mechanisms have been attributed antigen-mediated cellular transformation or replication, date, no studies investigated any potential link between T antigen highly metastatic nature MCC. Here we use...
Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic associated with various AIDS-related malignancies. Like other herpesviruses, multiple processes required for KSHV lytic replication, including viral transcription, DNA synthesis and capsid assembly occur in virus-induced intranuclear structures, termed replication transcription compartments (RTCs). Here we utilised a novel methodology, combining subcellular fractionation quantitative proteomics, to identify cellular proteins...
Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They the aetiological agents almost all cervical cancers as well sub-set other anogenital and head neck cancers. Hijacking host cellular pathways is essential for virus pathogenesis; however, challenge remains to identify key targets define their contribution HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating function transcription factor YAP. Increased YAP expression has been...
Abstract Historically, ribosomes were viewed as unchanged homogeneous macromolecular machines with no regulatory capacity for mRNA translation. An emerging concept is that heterogeneity of ribosomal composition exists, exerting a function or specificity in translational control. This supported by recent discoveries identifying compositionally distinct specialised actively regulate Viruses lack their own machinery and impose high demands on the host during replication. We explore possibility...
Human papillomaviruses (HPVs) cause most cervical cancers and an increasing number of anogenital oral carcinomas, with cases caused by HPV16 or HPV18. HPV hijacks host signalling pathways to promote carcinogenesis. Understanding these interactions could permit identification much-needed therapeutics for HPV-driven malignancies. The Hippo pathway is important in HPV+ cancers, the downstream effector YAP playing a pro-oncogenic role. In contrast, significance its paralogue TAZ remains largely...
The Kaposi's sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) protein regulates the latent-lytic switch by transactivating a variety of KSHV lytic cellular promoters. RTA is novel E3 ubiquitin ligase that targets number transcriptional repressor proteins for degradation proteasome pathway. Herein, we show interacts with Hey1. We demonstrate Hey1 target RTA-mediated ubiquitination subsequently degraded proteasome. Moreover, Cys-plus-His-rich region within...
Artificial binding proteins are tools for exploring cellular processes dependent on SUMOylation.
The nucleolus is the largest subnuclear structure and plurifunctional in nature. Here, we demonstrate that nucleolar localization of a key herpesvirus regulatory protein essential for its role virus mRNA nuclear export. saimiri ORF57 nucleocytoplasmic shuttle conserved all herpesviruses orchestrates export viral intronless mRNAs. We expression induces redistribution human TREX (transcription/export) proteins are involved Moreover, describe previously unidentified signal within composed two...
The herpesvirus proteins HSV-1 ICP27 and HVS ORF57 promote viral mRNA export by utilizing the cellular machinery. This function is triggered binding to of transcription-export (TREX) complex, in particular REF/Aly which directs TAP/NFX1 pathway and, subsequently, nuclear pore for cytoplasm. Here we have determined structure REF-ICP27 interaction interface at atomic-resolution provided a detailed comparison interfaces between ICP27, REF using solution-state NMR. Despite absence any obvious...
The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the factor, TAP, via a direct interaction with adaptor, Aly. Intriguingly however, depletion of Aly only leads to modest reduction in export, suggesting existence additional adaptor proteins. In order efficiently Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from nucleus, KSHV ORF57 protein recruits onto viral allowing access TAP-mediated pathway. Similarly mRNAs. Herein, we identify novel between...
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of sarcoma (KS) and primary effusion lymphoma (PEL), which are aggressive malignancies associated with immunocompromised patients. For many non-viral malignancies, therapeutically targeting ubiquitin proteasome system (UPS) has been successful. Likewise, laboratory studies have demonstrated that inhibition UPS might provide a promising avenue for treatment KSHV-associated diseases. The largest class E3 ligases cullin-RING...
A fifth of worldwide cancer cases have an infectious origin, with viral infection being the foremost. One such is Merkel cell carcinoma (MCC), a rare but aggressive skin malignancy. In 2008, polyomavirus (MCPyV) was discovered as causative agent MCC. It found clonally integrated into majority MCC tumours, which require MCPyV oncoproteins to survive. Since its discovery, research has begun reveal molecular virology MCPyV, well how it induces tumourigenesis. thought be common commensal, at low...