A5002088426- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- MicroRNA in disease regulation
- Bacteriophages and microbial interactions
- Malaria Research and Control
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- Peptidase Inhibition and Analysis
- Cancer-related molecular mechanisms research
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- Receptor Mechanisms and Signaling
- HIV Research and Treatment
- Bone Tissue Engineering Materials
- Genomics and Phylogenetic Studies
- Antimicrobial Peptides and Activities
- Mitochondrial Function and Pathology
- Computational Drug Discovery Methods
- Biotin and Related Studies
- Chromosomal and Genetic Variations
Washington University in St. Louis
2016-2025
Johns Hopkins University
2010-2013
Howard Hughes Medical Institute
2010-2013
Johns Hopkins Medicine
2011
Max Planck Institute for Developmental Biology
2005-2010
Max Planck Society
2006-2008
The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and extreme record of pesticide resistance. Here we present the completely sequenced annotated genome, representing first complete chelicerate genome. At 90 megabases T. has smallest arthropod Compared other arthropods, genome shows unique changes in hormonal environment organization Hox complex, also reveals evolutionary innovation silk production. We find strong signatures polyphagy...
microRNAs (miRNAs) regulate gene expression through translational repression and/or messenger RNA (mRNA) deadenylation and decay. Because translation, deadenylation, decay are closely linked processes, it is important to establish their ordering thus define the molecular mechanism of silencing. We have investigated kinetics these events in miRNA-mediated silencing by using a Drosophila S2 cell-based controllable system show that mRNAs with both natural engineered 3' untranslated regions...
Abstract Translation initiation is a major rate-limiting step for protein synthesis. However, recent studies strongly suggest that the efficiency of synthesis additionally regulated by multiple factors impact elongation phase. To assess influence early on synthesis, we employed library more than 250,000 reporters combined with in vitro and vivo expression assays. Here report identity amino acids encoded codons 3 to 5 yield. This effect independent tRNA abundance, translation efficiency, or...
Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of into an ORF diminishes expression more than AAG codons. Kinetic studies in E. coli reveal differential production results pausing on consecutive AAA-lysines followed by ribosome sliding homopolymeric A sequence. Translation a cell-free system demonstrates...
Conserved poly(A) tracks in coding regions are attenuators of translation.
Synthetic mRNA technology is a promising avenue for treating and preventing disease. Key to the incorporation of modified nucleotides such as N1-methylpseudouridine (m1Ψ) decrease immunogenicity RNA. However, relatively few studies have addressed effects on decoding process. Here, we investigate effect m1Ψ related modification pseudouridine (Ψ) translation. In reconstituted system, find that does not significantly alter accuracy. More importantly, do detect an increase in miscoded peptides...
The identification of genetic mechanisms underlying evolutionary change is critical to our understanding natural diversity, but presently limited by the lack and genomic resources for most species. Here, we present a new comparative approach that can be applied broad taxonomic sampling nonmodel species investigate basis change. Using analysis pipeline, show duplication divergence fgfr1a correlated with reduction scales within fishes genus Phoxinellus. As parallel mechanism observed in...
RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3' untranslated regions (UTRs) of mRNAs, regulate stability translation efficiency. With the identification numerous RBPs miRNAs, there is an urgent need for new technologies to dissect function cis-acting elements miRNAs. We describe post-transcriptional regulatory element sequencing (PTRE-seq), a massively parallel method assaying target miRNAs RBPs. use PTRE-seq sequence preferences interactions between The sites...
Abstract MicroRNAs are well known regulators of mRNA stability and translation. However, the magnitude both translational repression decay induced by miRNA binding varies greatly between targets. This can be result cis trans factors that affect or action. We set out to address this issue studying how various characteristics miRNA-mediated repression. Using a dual luciferase reporter system, we systematically analyzed ability selected elements modulate found changing 3′UTR miRNA-targeted...
is a causative agent of human malaria. Sixty percent mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite hosts and other sequenced organisms. Recent studies indicate polyA cause ribosome stalling frameshifting, triggering mRNA surveillance pathways attenuating protein synthesis. Here, we show that
Plasmodium falciparum, the malaria-causing parasite, is a leading cause of infection-induced deaths worldwide. The preferred treatment approach artemisinin-based combination therapy, which couples fast-acting artemisinin derivatives with longer-acting drugs, such as lumefantrine, mefloquine, and amodiaquine. However, urgency for new treatments has risen due to parasite's growing resistance existing therapies. In this study, common characteristic P. falciparum proteome—stretches poly-lysine...
Abstract De novo mutations cause a variety of neurodevelopmental disorders including autism. Recent whole genome sequencing from individuals with autism has shown that many de also occur in untranslated regions (UTRs) genes, but it is difficult to predict sequence alone which are functional, let causal. Therefore, we developed high throughput assay screen the transcriptional and translational effects 997 variants 5′UTR patient mutations. This successfully enriched for elements alter reporter...
The dynamic host-parasite mechanisms underlying hookworm infection establishment and maintenance in mammalian hosts remain poorly understood but are primarily mediated by hookworm’s excretory/secretory products (ESPs), which have a wide spectrum of biological functions. We used ultra-high performance mass spectrometry to comprehensively profile compare female male ESPs from the zoonotic human Ancylostoma ceylanicum, is natural parasite dogs, cats, humans. improved genome annotation,...
Abstract Hypomorphic mutations are a valuable tool for both genetic analysis of gene function and synthetic biology applications. However, current methods to generate hypomorphic limited specific organism, change expression unpredictably, or depend on changes in spatial-temporal the targeted gene. Here we present simple predictable method model organisms by targeting translation elongation. Adding consecutive adenosine nucleotides, so-called polyA tracks, coding sequence interest will...