A5052979052- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- Viral-associated cancers and disorders
- Nanopore and Nanochannel Transport Studies
- HVDC Systems and Fault Protection
- Cytomegalovirus and herpesvirus research
- Ion-surface interactions and analysis
- Chromosomal and Genetic Variations
- Lymphoma Diagnosis and Treatment
- Cardiac Structural Anomalies and Repair
- Natural Language Processing Techniques
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- CRISPR and Genetic Engineering
- Receptor Mechanisms and Signaling
- Genetic factors in colorectal cancer
- Fuel Cells and Related Materials
- Biotin and Related Studies
- Antimicrobial Peptides and Activities
- Molecular Biology Techniques and Applications
- Machine Learning in Bioinformatics
University of Leeds
2019-2025
Institute of Structural and Molecular Biology
2023
University of Sussex
2014
University of California, Berkeley
2010-2013
Innovative Genomics Institute
2011
University of Cambridge
2010
Thousands of small Open Reading Frames (smORFs) with the potential to encode peptides fewer than 100 amino acids exist in our genomes. However, number smORFs actually translated, and their molecular functional roles are still unclear. In this study, we present a genome-wide assessment smORF translation by ribosomal profiling polysomal fractions Drosophila. We detect two types bound multiple ribosomes thus undergoing productive translation. The ‘longer’ around 80 resemble canonical proteins...
The spliceosome, a dynamic assembly of proteins and RNAs, catalyzes the excision intron sequences from nascent mRNAs. Recent work has suggested that activity composition spliceosome are regulated by ubiquitination, but underlying mechanisms have not been elucidated. Here, we report spliceosomal Prp19 complex modifies Prp3, component U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. chains increase affinity Prp3 for U5 snRNP Prp8, thereby allowing stabilization U4/U6.U5 snRNP. is...
Abstract Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length UTRs and the composition regulatory elements within them known to vary substantially across genes, but little is about reasons for this variation in humans. Here, we set out determine whether variation, specifically 5’UTRs, correlates with gene dosage sensitivity. Results We investigate 5’UTR length, number alternative transcription start sites, potential splicing, type...
A major scientific drive is to characterize the protein-coding genome as it provides primary basis for study of human health. But fundamental question remains: what has been missed in prior genomic analyses? Over past decade, translation non-canonical open reading frames (ncORFs) observed across cell types and disease states, with implications proteomics, genomics, clinical science. However, impact ncORFs limited by absence a large-scale understanding their contribution proteome. Here, we...
Transcription and pre-mRNA alternative splicing are highly regulated processes that play major roles in modulating eukaryotic gene expression. It is increasingly apparent other pathways of RNA metabolism, including small biogenesis, can regulate these processes. However, a direct link between has remained elusive. Here we show the pathway protein Argonaute-2 (Ago-2) regulates patterns specific transcripts Drosophila nucleus using genome-wide methods conjunction with RNAi cell culture Ago-2...
Ribosomes have long been thought of as homogeneous macromolecular machines, but recent evidence suggests they are heterogeneous and could be specialised to regulate translation. Here, we characterised ribosomal protein heterogeneity across 4 tissues Drosophila melanogaster. We find that testes ovaries contain the most ribosome populations, which occurs through a combination paralog-enrichment paralog-switching. solved structures ribosomes purified from in vivo by cryo-EM, revealing...
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...
Ribosomal profiling has revealed the translation of thousands sequences outside annotated protein-coding genes, including small open reading frames less than 100 codons, and translational regulation many genes. Here we present an improved version Poly-Ribo-Seq apply it to Drosophila melanogaster embryos extend catalog in vivo translated ORFs, reveal both canonical ORFs from mRNAs across embryogenesis.We obtain highly correlated samples five embryonic stages, with nearly 500 million putative...
The expression of long noncoding RNAs is highly enriched in the human nervous system. However, function neuronal lncRNAs cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand interaction with machinery functional consequences during differentiation SH-SY5Y cells. We discovered 237 cytoplasmic up-regulated early differentiation, 58%–70% which are associated polysome complexes. Among these polysome-associated lncRNAs, find 45 small...
Open AccessMoreSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations Share ShareShare onFacebookTwitterLinked InRedditEmail Cite this article Aspden Julie, Faller William James, Barna Maria and Lund Anders 2025Ribosome heterogeneity specializationPhil. Trans. R. Soc. B38020230375http://doi.org/10.1098/rstb.2023.0375SectionOpen AccessIntroductionRibosome specialization Julie https://orcid.org/0000-0002-8537-6204 School of Molecular Cellular Biology, Faculty Biological...
Nanopores hold great potential for the analysis of complex biological molecules at single-entity level. One particularly interesting macromolecular machine is ribosome, responsible translating mRNAs into proteins. In this study, we use a solid-state nanopore to fingerprint 80S ribosomes and polysomes from human neuronal cell line andDrosophila melanogaster cultured cells ovaries. Specifically, show that peak amplitude dwell time characteristics are distinct can be used discriminate in mixed...
The epitranscriptomic modification N6-methyladenosine (m6A) is a ubiquitous feature of the mammalian transcriptome. It modulates mRNA fate and dynamics to exert regulatory control over numerous cellular processes disease pathways, including viral infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation from latent phase leads redistribution m6A topology upon both mRNAs within infected cells. Here we investigate role in transcripts upregulated during KSHV lytic replication. Our...
The regulated head-to-tail expression of Hox genes provides a coordinate system for the activation specific programmes cell differentiation according to axial level. Recent work indicates that can be via RNA processing but underlying mechanisms and biological significance this form regulation remain poorly understood. Here we explore these issues within developing Drosophila central nervous (CNS). We show pan-neural RNA-binding protein (RBP) ELAV (Hu antigen) regulates patterns gene...
Our understanding of mRNA translation and its regulation has been transformed by the development ribosome profiling. This approach relies upon RNase footprinting translating ribosomes in a precise manner to generate an accurate snapshot positions with nucleotide resolution. Here we tested variety conditions, which contribute preciseness therefore success We found that NaCl concentration, RNaseI source, amount, temperature all contributed quality human neuroblastoma SH-SY5Y cells. These ideal...
RNA sequence elements involved in the regulation of pre-mRNA splicing have previously been identified vertebrate genomes by computational methods. Here, we apply such approaches to predict regulatory Drosophila melanogaster and compare them with found human, mouse, pufferfish genomes. We 99 putative exonic enhancers (ESEs) 231 intronic (ISEs) enriched near weak 5' 3' splice sites constitutively spliced introns, distinguishing between those short long introns. that a significant proportion...
An intron is an extended genomic feature whose function requires multiple constrained positions-donor and acceptor splice sites, a branch point, polypyrimidine tract suitable splicing enhancers-that may be distributed over hundreds or thousands of nucleotides. New introns are therefore unlikely to emerge by incremental accumulation functional sub-elements. Here we demonstrate that can created de novo in single step segmental duplication. This experiment recapitulates vivo the birth arose...
Loss of functional RAB18 causes the autosomal recessive condition Warburg Micro syndrome. To better understand this disease, we used proximity biotinylation to generate an inventory potential effectors. A restricted set 28 interactions were dependent on binary RAB3GAP1-RAB3GAP2 RAB18-guanine nucleotide exchange factor complex. Twelve these are supported by prior reports, and have directly validated novel with SEC22A, TMCO4, INPP5B. Consistent a role for in regulating membrane contact sites,...
Abstract Background Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length UTRs and the composition regulatory elements within them known to vary substantially across genes, but little is about reasons for this variation in humans. Here, we set out determine whether variation, specifically 5’UTRs, correlates with gene dosage sensitivity. Results We investigated 5’UTR length, number alternative transcription start sites, potential splicing, type...
Abstract Gene fusion occurs when two or more individual genes with independent open reading frames becoming juxtaposed under the same frame creating a new fused gene. A small number of gene fusions described in detail have been associated novel functions, for example, hominid-specific PIPSL gene, TNFSF12, and TWE-PRIL family. We use Sequence Similarity Networks species level comparisons great ape genomes to identify 45 that emerged by transcriptional readthrough, is, transcription-derived...