A5006646678- RNA modifications and cancer
- Trypanosoma species research and implications
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Research on Leishmaniasis Studies
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Evolution and Genetic Dynamics
- CRISPR and Genetic Engineering
- HVDC Systems and Fault Protection
- Parasitic Infections and Diagnostics
- Viral Infections and Immunology Research
- Viral-associated cancers and disorders
- Chromosomal and Genetic Variations
- Cytomegalovirus and herpesvirus research
- Extracellular vesicles in disease
- Circular RNAs in diseases
- Endoplasmic Reticulum Stress and Disease
- Biochemical and Molecular Research
- Cardiomyopathy and Myosin Studies
- Cancer-related gene regulation
- Cardiac Structural Anomalies and Repair
- Signaling Pathways in Disease
- Plant Virus Research Studies
- Cardiovascular Effects of Exercise
Bar-Ilan University
2016-2025
Weizmann Institute of Science
2022-2025
Goodman (Japan)
2020
Madurai Kamaraj University
2015-2018
Bharathidasan University
2014
Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it reversible and not associated with cardiomyocyte death, considered as a natural tactic to prevent dysfunction failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role physiological largely unexplored. Hence, this study aimed at revealing global expression profile miRNAs hypertrophy. Chronic swimming protocol continuously for eight...
Leishmania is the causative agent of cutaneous and visceral diseases affecting millions individuals worldwide. Pseudouridine (Ψ), most abundant modification on rRNA, changes during parasite life cycle. Alterations in level a specific Ψ helix 69 (H69) affected ribosome function. To decipher molecular mechanism this phenotype, we determine structure ribosomes lacking single its parental strain at ∼2.4–3 Å resolution using cryo-EM. Our findings demonstrate significance H69 to importance for...
The protozoan parasite Trypanosoma brucei, which causes devastating diseases in humans and animals sub-Saharan Africa, undergoes a complex life cycle between the mammalian host blood-feeding tsetse fly vector. However, little is known about how performs most molecular functions such different environments. Here, we provide evidence for intriguing possibility that pseudouridylation of rRNA plays an important role capacity to transit insect midgut bloodstream. Briefly, mapped pseudouridines...
Abstract The parasite Trypanosoma brucei, the causative agent of sleeping sickness, cycles between an insect and a mammalian host. Here, we investigated presence pseudouridines (Ψs) on spliceosomal small nuclear RNAs (snRNAs), which may enable growth at very different temperatures characterizing two hosts. To this end, performed first high-throughput mapping snRNA Ψs by RNA Ψ-seq. analysis revealed 42 T. brucei snRNAs, is highest number reported so far. We show that trypanosome protein...
Significance Chromosome and gene copy number variations often correlate with the evolution of microbial cancer drug resistance, thus causing important human mortality. How genome instability is harnessed to generate beneficial phenotypes how deleterious dosage effects are compensated remain open questions. The protist pathogen Leishmania exploits regulate expression via changes. Using these parasites as a unique model system, we uncover complex epistatic interactions between compensatory...
The parasite Trypanosoma brucei causes African sleeping sickness that is fatal to patients if untreated. Parasite differentiation from a replicative slender form into quiescent stumpy promotes host survival and transmission. Long noncoding RNAs (lncRNAs) are known regulate cell in other eukaryotes. To determine whether lncRNAs also involved differentiation, we used RNA sequencing survey the T. genome, identifying 1428 previously uncharacterized lncRNA genes. We find grumpy key regulator...
The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver fitness gain response to environmental change or chemotherapy. How genome generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting vitro culture. Phenotypic...
Abstract Trypanosomes are protozoan parasites that cycle between insect and mammalian hosts the causative agent of sleeping sickness. Here, we describe changes pseudouridine (Ψ) modification on rRNA in two life stages parasite using four different genome-wide approaches. CRISPR-Cas9 knock-outs all snoRNAs guiding Ψ helix 69 (H69) large subunit were lethal. A single knock-out a snoRNA Ψ530 H69 altered composition 80S monosome. These specifically affected translation only subset proteins. This...
Genetic feedback control represents a central paradigm in regulation of biological systems and their response to environmental change. Vector-borne pathogens have evolved complex developmental programs adapt very distinct host environments, but the relevance stage differentiation remains be elucidated. Here we address this open question trypanosomatid parasite Leishmania that shows constitutive gene transcription, thus providing unique model system assess post-transcriptional mechanisms...
The protozoan parasite Trypanosoma brucei undergoes a complex life cycle, moving between its mammalian host and the blood-feeding tsetse fly vector. two major surface proteins expressed by procyclic forms in insect midgut, EP GPEET procyclin, are transcribed from polycistronic transcription unit RNA polymerase I. Here we identify long non-coding RNA, TblncRNA-23, that is encoded procyclin genes. TblncRNA-23 localizes to nucleolus also associates with polysomes. Overexpression of down...
The parasite Trypanosoma brucei cycles between insect and mammalian hosts, is the causative agent of sleeping sickness. Here, we performed genome-wide mapping 2'-O-methylations (Nms) on trypanosome rRNA using three high-throughput sequencing methods; RibOxi-seq, RiboMeth-seq 2'-OMe-seq. This first study approaches from same species showing discrepancy among methods. RibOxi-seq detects all sites, but only method to evaluate level a single Nm site. revealed at least ninety-nine Nms guided by...
In trypanosomes, in contrast to most eukaryotes, the large subunit (LSU) ribosomal RNA is fragmented into two and four small RNAs (srRNAs) pieces, this additional processing likely requires trypanosome-specific factors. Here, we examined role of 10 abundant nucleolar (snoRNAs) involved rRNA processing. We show that each snoRNA LSU associates with factors engaged either early or late biogenesis steps. Five these snoRNAs interact intervening sequences precursor, whereas others only guide...
The parasite Trypanosoma brucei cycles between an insect and a mammalian host is the causative agent of sleeping sickness. Here, we performed high-throughput mapping pseudouridines (Ψs) on mRNA from two life stages parasite. analysis revealed ~273 Ψs, including developmentally regulated Ψs that are guided by homologs pseudouridine synthases (PUS1, 3, 5, 7). Mutating U undergoes pseudouridylation in 3' UTR valyl-tRNA synthetase destabilized level. To investigate mechanism which Ψ affects...
The vault ribonucleoprotein (RNP), comprising RNA (vtRNA) and telomerase-associated protein 1 (TEP1), is found in many eukaryotes. However, previous studies of vtRNAs, for example mammalian cells, have failed to reach a definitive conclusion about their function. vtRNAs are related Y RNAs, which complexed with Ro influence Ro's function noncoding (ncRNA) quality control processing. In Trypanosoma brucei, the small TBsRNA-10 was first described survey ncRNA repertoire this organism. Here, we...
The parasite Trypanosoma brucei is the causative agent of sleeping sickness and cycles between insect mammalian hosts. appears to lack conventional transcriptional regulation protein coding genes, mRNAs are processed from polycistronic transcripts by concerted action trans-splicing polyadenylation. Regulation mRNA function mediated mainly RNA binding proteins affecting stability translation. In this study, we describe identification 62 non-coding (nc) RNAs that developmentally regulated...
During spaceflight, astronauts are exposed to various physiological and psychological stressors that have been associated with adverse health effects. Therefore, there is an unmet need develop novel diagnostic tools predict early alterations in astronauts’ health. Small nucleolar RNA (snoRNA) a type of short non-coding (60–300 nucleotides) known guide 2′-O-methylation (Nm) or pseudouridine (ψ) ribosomal (rRNA), small nuclear (snRNA), messenger (mRNA). Emerging evidence suggests dysregulated...