Biology subjects

Teleman, A.

Publications and source records attributed to Teleman, A..

4 recordsLinked to original sources

bioRxiv2024

Expression dynamics of long non-coding RNAs during imaginal disc development and regeneration in Drosophila

The discovery of functional long non-coding RNAs (lncRNAs) changed their initial concept as transcriptional noise. LncRNAs have been found to participate in the regulation of multiple biological processes, including chromatin structure, gene expression, splicing, and mRNA degradation and translation. However, functional studies of lncRNAs are hindered by the usual lack of phenotypes upon deletion or inhibition. Here, we used Drosophila imaginal discs as a model system to identify lncRNAs involved in development and regeneration. We examined a subset of lncRNAs expressed in the wing, leg, and eye disc development. Additionally, we analyzed transcriptomic data from regenerating wing discs to profile the expression pattern of lncRNAs during tissue repair. We focused on the lncRNA CR40469, which is upregulated during regeneration. We generated CR40469 mutant flies that developed normally but showed impaired wing regeneration upon the induction of cell death. The ability of these mutants to regenerate was restored by the ectopic expression of CR40469. Furthermore, we found that the lncRNA CR34335 has a high degree of sequence similarity with CR40469 and can partially compensate for its function during regeneration in the absence of CR40469. Our findings point to a potential role of the lncRNA CR40469 in trans during the response to damage in the wing imaginal disc.

developmental biology↗

bioRxiv2023

Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs

Despite a strong rationale for why cancer cells are susceptible to redox-targeting drugs, such drugs often face tumor resistance or dose-limiting toxicity in preclinical and clinical studies. An important reason is the lack of specific biomarkers to better select susceptible cancer entities and stratify patients. Using a large panel of lung cancer cell lines, we identified a set of "antioxidant-capacity" biomarkers (ACB), which were tightly repressed, partly by STAT3 and STAT5A/B in sensitive cells, rendering them susceptible to multiple redox-targeting and ferroptosis-inducing drugs. Contrary to expectation, constitutively low ACB expression was not associated with an increased steady state level of reactive oxygen species (ROS) but a high level of nitric oxide, which is required to sustain high replication rates. Using ACBs, we identified cancer entities with a high percentage of patients with favorable ACB expression pattern, making it likely that more responders to ROS-inducing drugs could be stratified for clinical trials.

cancer biology↗

bioRxiv2020

G3BP1 tethers the TSC complex to lysosomes and suppresses mTORC1 in the absence of stress granules

G3BP1 (Ras GTPase-activating protein-binding protein 1) is widely recognized as a core component of stress granules (SG), non-membranous RNA-protein-assemblies required for cellular survival under stress. We report that in the absence of SG, G3BP1 acts as lysosomal anchor of the Tuberous Sclerosis Complex (TSC) protein complex. By tethering the TSC complex to lysosomes, G3BP1 suppresses signaling through the metabolic master regulator mTORC1 (mechanistic target of rapamycin complex 1). Like the known TSC complex subunits, G3BP1 suppresses phenotypes related to mTORC1 hyperactivity in the context of tumors and neuronal dysfunction. Thus, G3BP1 is not only a core component of SG but also a key element of lysosomal TSC-mTORC1 signaling. HighlightsThe bona fide stress granule component G3BP1 O_LIis a key element of the TSC-mTORC1 signaling axis. C_LIO_LItethers the TSC complex to lysosomes. C_LIO_LIprevents mTORC1 hyperactivation by metabolic stimuli. C_LIO_LIsuppresses mTORC1-driven cancer cell motility and epileptiform activity. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/044081v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@77cb4forg.highwire.dtl.DTLVardef@c4d1a0org.highwire.dtl.DTLVardef@19e83acorg.highwire.dtl.DTLVardef@1d6a378_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2017

Sorting & Sequencing Flies By Size: Identification Of Novel TOR Regulators And Parameters For Successful Sorting

As DNA sequencing throughput increases, novel strategies for discovering genes that affect traits of interest become available. One strategy starts with a population of animals and selects individuals over multiple generations for a particular trait. Subsequent whole genome sequencing should identify loci affecting this trait. We apply this strategy by sorting flies for wing length over 18 generations, obtaining two populations that differ in wing length by 20%. Flies with longer wings had increased overall body sizes and elevated TOR activity, suggesting that genetic variation targets TOR signaling to influence body size. High-throughput sequencing of big and small flies identified thousands of single nucleotide polymorphisms that differed between the two populations, leading us to identify five novel regulators of TOR signaling. Surprisingly, stochastic simulations of the process show that large fractions of the genetic differences between the big and small flies are probably biological false positives, selected by chance by random drift. We employ these computer simulations to identify experimental setup parameters to improve the signal-to-noise ratio for successfully running sort-and-sequence experiments - a resource which will hopefully be useful for the community.

genetics↗