A5024199145- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Hereditary Neurological Disorders
- RNA regulation and disease
- DNA and Nucleic Acid Chemistry
- Plant Disease Resistance and Genetics
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Peptidase Inhibition and Analysis
- Neurogenetic and Muscular Disorders Research
- Molecular Sensors and Ion Detection
- Cancer, Hypoxia, and Metabolism
- Superconducting Materials and Applications
- Neurotransmitter Receptor Influence on Behavior
- Evolution and Genetic Dynamics
- Neuroscience and Neuropharmacology Research
- Genomics and Phylogenetic Studies
- HVDC Systems and Fault Protection
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
Broad Institute
2020-2023
Harvard University
2019-2023
University of Chicago
2018-2021
Howard Hughes Medical Institute
2020
University of Warsaw
2015-2018
University of Kentucky
2016
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2015
University of Waterloo
2014-2015
College of Europe, Warsaw
2015
Significance C/D box small nucleolar RNAs (SNORDs) are abundant, short, nucleoli-residing, noncoding that guide the methyltransferase fibrillarin to perform 2′- O -methylation of target RNAs. We identified 29 SNORDs present in a fibrillarin-containing fraction as well fibrillarin-free enriched spliceosomes. One these SNORDs, SNORD27 , directs rRNA methylation and regulates alternative pre-mRNA splicing (AS) E2F7 pre-mRNA, transcriptional repressor cell cycle-regulated genes. likely AS by...
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, arises from survival motor neuron (SMN) protein insufficiency resulting
Eukaryotic transfer RNAs (tRNA) contain on average 13 modifications that perform a wide range of roles in translation and the generation tRNA fragments regulate gene expression. Queuosine (Q) modification occurs wobble anticodon position tRNAs for amino acids His, Asn, Tyr, Asp. In eukaryotes, Q is fully dependent diet or gut microbiome multicellular organisms. Despite decades study, cellular remain to be elucidated. Here we show human cells, specifically protects its cognate His Asn against...
In vitro selection of RNA-cleaving DNAzymes was performed using three heavy lanthanide ions (Ln3+): Ho3+, Er3+ and Tm3+. The resulting sequences were aligned together about half the library contained a new family DNAzyme. These have simple loop structure, they are active only with seven Ln3+. Among tested non-lanthanide ions, Y3+ induced cleavage even Pb2+ failed to cleave, suggesting very high specificity. A representative DNAzyme, Tm7, has sigmoidal metal binding curve Hill coefficient 3,...
Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification human cells depends on gut microbiome because product queuine is required for its installation by enzyme Q ribosyltransferase catalytic subunit 1 (QTRT1) encoded genome. Queuine a micronutrient from diet and microbiome. Although has been studied long time regarding properties decoding fragment generation, how QTRT1 affects tumorigenesis...
Aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) are the largest protein family causatively linked to neurodegenerative Charcot–Marie–Tooth (CMT) disease. Dominant mutations cause disease, and studies of CMT disease-causing mutant glycyl-tRNA synthetase (GlyRS) tyrosyl-tRNA (TyrRS) showed their create neomorphic structures consistent with a gain-of-function mechanism. In contrast, based on haploid yeast model, loss aminoacylation function was reported for disease mutants in histidyl-tRNA...
A trivalent lanthanide (Ln(3+))-dependent RNA-cleaving DNAzyme, Ce13d, was recently isolated via in vitro selection. Ce13d is active the presence of all Ln(3+) ions. Via introduction a single phosphorothioate (PS) modification at cleavage site, its activity with decreases while thiophilic metals can activate this DNAzyme. This property unique to and not found many other tested DNAzymes. suggests well-defined but general metal binding site. Herein, systematic study PO substrate (using Ce(3+))...
Abstract Small nucleolar RNA (snoRNA) are conserved and essential non-coding that transcribed by Polymerase II (Pol II). Two snoRNA classes, formerly distinguished their structure ribonucleoprotein composition, act as guide to target such ribosomal RNA, thereby introduce specific modifications. We have studied the 5ʹend processing of individually in S. cerevisiae define role biogenesis functionality. Here we show pre-snoRNA endonuclease Rnt1 occurs co-transcriptionally with removal m 7 G cap...
Queuosine (Q) is a conserved tRNA modification in bacteria and eukaryotes. Eukaryotic Q-tRNA occurs through replacing the guanine base with scavenged metabolite queuine at wobble position of tRNAs G34U35N36 anticodon (Tyr, His, Asn, Asp) by QTRT1/QTRT2 heterodimeric enzyme encoded genome. In humans, Q-modification tRNATyr tRNAAsp are further glycosylated galactose mannose, respectively. Although galactosyl-Q (galQ) mannosyl-Q (manQ) can be measured LC/MS approaches, difficulty detecting...
Significance Charcot-Marie-Tooth disease (CMT) is a devastating motor and sensory neuropathy with an estimated 100,000 afflicted individuals in the US. Unexpectedly, aminoacyl-tRNA synthetases are largest disease-associated protein family. A natural explanation that associated weak translation or mistranslation (caused by editing defects). However, our results six different disease-causing mutants AlaRS ruled out defects aminoacylation as causal factors. Instead, specific mutant proteins...
The development of addiction is associated with a dysregulation glutamatergic transmission in the brain reward circuit. α isoform calcium/calmodulin-dependent kinase II (αCaMKII) one key proteins that regulates structural and functional plasticity synapses. αCaMKII activity can be controlled by autophosphorylation threonine 286. role this regulation addiction-related behaviors has been proposed but still poorly understood. Here, using autophosphorylation-deficient mutant mice (T286A), we...
<title>Abstract</title> Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification human cells depends on gut microbiome because product queuine is required for its installation by enzyme ribosyltransferase catalytic subunit 1 (QTRT1) encoded genome. Although has been studied a long time regarding properties decoding and fragment generation, how QTRT1 affects tumorigenesis still poorly understood....
Queuosine (Q) is a hypermodified base in the wobble anticodon position of tRNAs coding for amino acids Tyr, His, Asn, and Asp.tRNA Q-modification introduced by queuine tRNAribosyltransferase (TGT) that replaces guanine at G34 these with modified base.tRNA widely distributed among prokaryotic eukaryotic organisms, but only bacteria synthesize Q-modified tRNA de novo.In mammals, Q-modifications strictly rely on presence gut microbiomes or diets to produce base.Despite decades study, cellular...
Small nucleolar RNAs (snoRNAs) are the best characterized non‐coding transcribed by RNA polymerase II. They produced as precursors, whose extended 3' ends trimmed exonucleolytically, whereas 5' either undergo combined endo‐ and exonucleolytic processing Rnt1 Rat1, respectively, or remain unchanged. In latter case, m 7 G cap becomes hypermethylated Tgs1. [figure1] cRT‐PCR analyses suggest that of snoRNA termini is tightly coupled. Inhibition end maturation, in rnt1Δ strain, cause accumulation...
Abstract Introduction: Glioblastoma (GBM) is the most frequent treatment resistant and poor prognosis primary brain tumor. Age-adjusted incidence among Caucasians approx. twice that of Africans. Genetic changes in ethnicity may represent druggable targets for development new treatments GBM. Chondroitin sulfate proteoglycan 4 (CSPG4) with sequence homology to neuron-glial-2 (NG2), henceforth CSPG4/NG2, a transmembrane upregulated GBM, resulting leaky neovasculature high cell proliferation,...