A5084592016- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Business, Innovation, and Economy
- Nanopore and Nanochannel Transport Studies
- CRISPR and Genetic Engineering
- Business, Education, Mathematics Research
- Urban Transport and Accessibility
- Literacy and Educational Practices
- Advanced Proteomics Techniques and Applications
- Spatial Cognition and Navigation
- Autophagy in Disease and Therapy
- Transportation Planning and Optimization
- Neurological diseases and metabolism
- Genomics and Chromatin Dynamics
- Muscle activation and electromyography studies
- Spacecraft Design and Technology
- Embedded Systems Design Techniques
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
Harvard University
2021-2024
Columbia University
2023-2024
Columbia University Irving Medical Center
2023
Broad Institute
2021-2022
Harvard Stem Cell Institute
2021-2022
Memorial Sloan Kettering Cancer Center
2013-2021
Kettering University
2014-2021
Massachusetts Institute of Technology
2012-2013
Highlights•Fly circular RNAs were annotated from >100 libraries and >10 billion total RNA-seq reads•Circular RNA properties include strong preference for long flanking introns•Circular are strongly biased to contain coding region conserved miRNA sites•Circular dominantly accumulate in the nervous system increase with ageSummaryCircularization was recently recognized broadly expand transcriptome complexity. Here, we exploit massive Drosophila RNA-sequencing data, >5 paired-end reads covering...
Abstract The conserved modification N 6 -methyladenosine (m A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study m A pathway. We first apply miCLIP map across embryogenesis, characterize its ‘writer’ complex, validate YTH ‘readers’ CG6422 YT521-B, generate mutants in five factors. While factors with additional roles splicing are lethal, A-specific viable but present certain developmental behavioural defects. Notably, facilitates master female...
The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal nanotechnology. Here we develop nanoparticles can be controllably triggered synthesize proteins. consist lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, DNA caged a photolabile protecting group. These particles served as nanofactories capable producing proteins green fluorescent protein (GFP)...
Abstract Epitranscriptomic modifications can impact behavior. Here, we used Drosophila melanogaster to study N 6 -methyladenosine (m A), the most abundant modification of mRNA. Proteomic and functional analyses confirm its nuclear (Ythdc1) cytoplasmic (Ythdf) YTH domain proteins as major m A binders. Assays short term memory in mutants reveal neural-autonomous requirements writers working via Ythdf, but not Ythdc1. Furthermore, A/Ythdf operate specifically mushroom body, center for...
Human pluripotent stem cells (hPSCs) are a powerful tool for disease modeling of hard-to-access tissues (such as the brain). Current protocols either direct neuronal differentiation with small molecules or use transcription-factor-mediated programming. In this study, we couple overexpression transcription factor Neurogenin2 (Ngn2) molecule patterning to differentiate hPSCs into lower induced motor neurons (liMoNes/liMNs). This approach induces canonical MN markers including MN-specific...
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, understand the unique molecular properties that may sensitize ETNs ALS, we performed RNA sequencing 79,169 single nuclei from cortices patients and controls. In both unaffected individuals, found significantly higher...
Rationally designed siRNA delivery materials that are enabled by lipid-modified aminoglycosides demonstrated. Leading identified able to self-assemble with into well-defined nanoparticles and induce efficient gene knockdown both in vitro vivo. Histology studies liver function tests reveal no apparent toxicity is caused these at doses over two orders of magnitude.
Accurate splice site selection is critical for fruitful gene expression. Recently, the mammalian EJC was shown to repress competing, cryptic, sites (SS). However, evolutionary generality of this remains unclear. Here, we demonstrate Drosophila suppresses hundreds functional cryptic SS, even though most bear weak splicing motifs and are seemingly incompetent. Mechanistically, directly conceals elements by virtue its position-specific recruitment, preventing aberrant SS definition....
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron loss accompanied cytoplasmic localization of TDP-43 proteins and their insoluble accumulations. Haploinsufficiency TBK1 has been found to associate with or cause ALS. However, the cell-autonomous mechanisms which reduced activity contributes human pathology remain elusive. Here, we generated cellular model harboring loss-of-function mutations gene editing that deficiency was...
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive loss of motor function. The eponymous spinal sclerosis observed at autopsy the result degeneration extratelencephalic neurons, Betz cells (ETNs, Cortico-Spinal Motor Neuron). It remains unclear why this neuronal subtype selectively affected. To understand unique molecular properties that sensitise these to ALS, we performed RNA sequencing 79,169 single nuclei from cortices patients and...
Although there is abundant evidence that individual microRNA (miRNA) loci repress large cohorts of targets, large-scale knockout studies suggest most miRNAs are phenotypically dispensable. Here, we identify a rare case developmental cell specification highly dependent on miRNA control an target. We observe binary fate choice in the Drosophila melanogaster peripheral sensory organ lineage controlled by non-neuronally expressed mir-279/996 cluster, with majority notum organs exhibiting...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22219-8
Intronic ratchet points (RPs) are abundant within long introns in the Drosophila genome and consist of juxtaposed splice acceptor donor (SD) sites. Although they appear to encompass zero-nucleotide exons, we recently clarified that intronic recursive splicing (RS) requires a cryptic exon at RP (an RS-exon), which is subsequently always skipped thus absent from mRNA. In addition, encodes smaller set expressed exons bearing features RS. Here, investigate mechanisms regulate choice between...
Abstract The roles of epitranscriptomic modifications in mRNA regulation have recently received substantial attention, with appreciation growing for their phenotypically selective impacts within the animal. We adopted Drosophila melanogaster as a model system to study m 6 A, most abundant internal modification mRNA. Here, we report proteomic and functional analyses fly A-binding proteins, confirming nuclear (YTHDC) cytoplasmic (YTHDF) YTH domain proteins major A binders. Since all core...
The self-assembled nanoparticles for siRNA delivery with lipid-modified aminoglycoside derivatives is described by Daniel G. Anderson and co-workers on page 4641. core-shell can protect from enzymatic degradation within the body subsequently deliver into cytoplasm of target cells. image courtesy Dr. Ning Zhang.
Summary DNA repair is directly performed by hundreds of core factors and indirectly regulated thousands others. We massively expanded a CRISPR inhibition Cas9-editing screening system to discover modulating homology directed (HDR) in the context ∼18’000 individual gene knockdowns. focused on CCAR1, poorly understood that we found reduced both HDR interstrand crosslink repair, phenocopying loss Fanconi Anemia pathway. CCAR1 abrogated FANCA protein without substantial reduction level its mRNA...