A5031956637- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- RNA regulation and disease
- Neuroscience and Neuropharmacology Research
- Cancer Immunotherapy and Biomarkers
- Receptor Mechanisms and Signaling
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Neurogenesis and neuroplasticity mechanisms
- CAR-T cell therapy research
- Angiogenesis and VEGF in Cancer
- Zebrafish Biomedical Research Applications
- Immune Cell Function and Interaction
- Signaling Pathways in Disease
- Retinal Development and Disorders
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Gene expression and cancer classification
Nara Institute of Science and Technology
2004-2024
Wellcome/MRC Cambridge Stem Cell Institute
2020
Medical Research Council
2020
University of Cambridge
2013-2019
Local mRNA translation mediates the adaptive responses of axons to extrinsic signals, but direct evidence that it occurs in mammalian CNS vivo is scant. We developed an axon-TRAP-RiboTag approach mouse allows deep-sequencing analysis ribosome-bound mRNAs retinal ganglion cell developing and adult retinotectal projection vivo. The embryonic-to-postnatal axonal translatome comprises evolving subset enriched genes with axon-specific roles, suggesting distinct steps axon wiring, such as...
Local translation regulates the axonal proteome, playing an important role in neuronal wiring and axon maintenance. How mRNAs are localized to specific subcellular sites for translation, however, is not understood. Here we report that RNA granules associate with endosomes along axons of retinal ganglion cells. RNA-bearing Rab7a late also ribosomes, real-time imaging reveals they local protein synthesis. We show often pause on mitochondria encoding proteins mitochondrial function translated...
Ribosome assembly occurs mainly in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding many ribosomal proteins (RPs) axons, far away from neuronal cell bodies. Here, we report a physical functional interaction between locally synthesized RPs ribosomes axon. We show that axonal RP is regulated through sequence motif, CUIC, forms an RNA-loop structure region immediately upstream initiation codon. Using imaging subcellular proteomics techniques,...
Axonal protein synthesis and degradation are rapidly regulated by extrinsic signals during neural wiring, but the full landscape of proteomic changes remains unknown due to limitations in axon sampling sensitivity. By combining pulsed stable isotope labeling amino acids cell culture with single-pot solid-phase-enhanced sample preparation, we characterized nascent proteome isolated retinal axons on an unparalleled rapid timescale (5 min). Our analysis detects 350 basally translated axonal...
Extrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling ribosomes to receptors has been proposed as a mechanism linking signals but it is not known how broadly this operates, nor whether can selectively regulate mRNA translation. We report that receptor-ribosome employed by multiple guidance cue and interaction mRNA-dependent. find different associate with distinct sets RNA-binding proteins. Cue stimulation
An international collaborative project has been proposed to inactivate all mouse genes in embryonic stem (ES) cells using a combination of random and targeted insertional mutagenesis techniques. Random gene trapping will be the first choice initial phase, gene-targeting experiments then carried out individually knockout remaining 'difficult-to-trap' genes. One most favored techniques is promoter trapping, which only disrupts actively transcribed Polyadenylation (poly-A) on other hand, can...
Upf1 is a highly conserved RNA helicase essential for nonsense-mediated mRNA decay (NMD), an quality-control mechanism that degrades aberrant mRNAs harboring premature termination codons (PTCs). For the activation of NMD, UPF1 interacts first with translation–terminating ribosome and then downstream exon–junction complex (EJC), which deposited at exon–exon junctions during splicing. Although activity indispensable its roles substrates have yet to be fully elucidated. Here we show stable...
DNA arrays are capable of profiling the expression patterns many genes in a single experiment. After finding gene interest array, however, labor-intensive gene-targeting experiments sometimes must be performed for vivo analysis function. With random trapping, on other hand, it is relatively easy to disrupt and retrieve hundreds genes/gene candidates mouse embryonic stem (ES) cells, but one could overlook potentially important gene-disruption events if only nucleotide sequences not trapped...
SUMMARY Ribosomes are known to be assembled in the nucleolus, yet recent studies have revealed robust enrichment and translation of mRNAs encoding ribosomal proteins (RPs) axons, far away from neuronal cell bodies. Using subcellular proteomics live-imaging, we show that locally synthesized RPs incorporate into axonal ribosomes a nucleolus-independent fashion. We RP is regulated through novel sequence motif, CUIC, forms RNA-loop structure region immediately upstream initiation codon....
Among the insertional mutagenesis techniques used in current international knockout mouse project (KOMP) on inactivation of all genes embryonic stem (ES) cells, random gene trapping has been playing a major role. Gene-targeting experiments have also performed to individually and conditionally remaining 'difficult-to-trap' genes. Here, we show that transcriptionally silent ES cells are severely underrepresented among randomly trapped KOMP. Our conditional poly(A)-trapping vector with common...
Abstract During neuronal wiring, extrinsic cues trigger the local translation of specific mRNAs in axons via cell surface receptors. The coupling ribosomes to receptors has been proposed as a mechanism linking signals but it is not known how broadly this operates, nor whether can selectively regulate mRNA translation. We report that receptor-ribosome employed by multiple guidance cue and interaction mRNA-dependent. find different bind distinct sets RNA-binding proteins. Cue stimulation...
Abstract X-linked inhibitor of apoptosis protein (XIAP) is a key suppressor apoptosis, major form programmed cell death critical for cellular differentiation, embryogenesis, and cancer development. Despite its importance, the upstream regulators regulatory elements XIAP are not well understood. This study provides evidence that zinc finger transcription factor Zbtb38, negative regulator regulates expression in Zbtb38 loss- gain-of-function experiments. Notably, overexpression rescued induced...
Abstract Introduction Programmed death-1 (PD-1) is a negative regulator of immune responses. Upon deletion PD-1 in mice, symptoms autoimmunity developed only after they got old. In model experiment cancer immunotherapy, was shown to prevent cytotoxic T lymphocytes from attacking cells that expressed neoantigens derived genome mutations. Furthermore, the larger number mutations led more robust anti-tumor responses blockade. To understand common molecular mechanisms underlying these findings,...
Abstract Aims programmed death-1 (PD-1) is a negative regulator of immune responses. Upon deletion PD-1 in mice, symptoms autoimmunity developed only after they got old. In model experiment cancer immunotherapy, was shown to prevent cytotoxic T lymphocytes from attacking cells that expressed neoantigens derived genome mutations. Furthermore, the larger number mutations led more robust anti-tumor responses blockade. order understand common molecular mechanisms underlying these findings, we...
Extrinsic cues trigger the local translation of specific mRNAs in growing axons via cell surface receptors. The coupling ribosomes to receptors has been proposed as a mechanism linking signals but it is not known how broadly this operates, nor whether can selectively regulate mRNA translation. We report that receptor-ribosome employed by multiple guidance cue and interaction mRNA-dependent. find different associate with distinct sets RNA-binding proteins. Cue stimulation Xenopus retinal...
Summary Random gene trapping is the application of insertional mutagenesis techniques that are conventionally used to inactivate protein‐coding genes in mouse embryonic stem (ES) cells. Transcriptionally silent not effectively targeted by conventional random techniques, thus we herein developed an unbiased poly (A) trap (UPATrap) method using a Tol2 transposon, which preferentially integrated into active rather than ES To achieve efficient at transcriptionally cells, generated new diphtheria...