Biology subjects

Glaser, F.

Publications and source records attributed to Glaser, F..

6 recordsLinked to original sources

bioRxiv2026

RBM25 exhibits distinct RNA- and chromatin-associated target programs in human embryonic stem cells

RNA-binding proteins (RBPs) are increasingly recognized to perform chromatin-associated functions in addition to their canonical roles in RNA regulation, yet how these activities are coordinated in human embryonic stem cells (hESCs) remain poorly understood. Here, we characterize distinct RNA- and chromatin-associated activities for RBM25 in hESCs. Transcriptome-wide profiling showed that RBM25 preferentially associates with transcripts involved in RNA processing and splicing, consistent with its canonical role as an RBP involved in post-transcriptional regulation. Genome-wide chromatin profiling further uncovered a distinct chromatin-associated program, with RBM25 occupying accessible promoters of actively expressed cell-cycle genes and introns predominantly associated with transcriptionally inactive neuronal genes. Interestingly, RBM25 chromatin-binding sites showed substantial co-occupancy with regions bound by the transcription factor CEBPZ in hESCs. We further show that RBM25 and CEBPZ physically interact and exhibit shared chromatin-binding patterns at both promoter and intronic regions. Importantly, reciprocal depletion experiments revealed that RBM25 is required for CEBPZ occupancy at CCAAT-containing promoters of highly expressed cell-cycle genes, whereas CEBPZ is not similarly required for RBM25 chromatin occupancy. Together, our findings establish RBM25 as a multifunctional factor with distinct roles in RNA processing and chromatin-associated regulation and reveal a context-dependent RBP-TF interaction that contributes to transcriptional regulation in hESCs.

molecular biology↗

bioRxiv2026

Population structure and genetic diversity of smooth newts (Lissotriton vulgaris) in North Tyrol, Austria: influences of allochthonous individuals and conservation implications

Amphibians are threatened worldwide by various environmental and anthropogenic factors, making non-invasive conservation studies particularly valuable. Newts are one example of a thus challenged amphibian group. In Austria, local population declines of newts have been observed, with the smooth newt (Lissotriton vulgaris) being strongly affected. In this study, skin swabs were used as a non-invasive method to gather DNA, combined with established microsatellite markers. We sampled 139 L. vulgaris individuals at ten sites in North Tyrol, Austria, and, for comparison, 22 L. vulgaris meridionalis individuals in Brixen, Italy. We genotyped all individuals and analysed their population structure. We demonstrate the presence of three distinct L. vulgaris population clusters and find differences in population structure between supposedly introduced allochthonous L. vulgaris individuals and autochthonous populations, as evidenced by differences in Bayesian clustering and elevated values of the fixation index FST. A captive population in a zoological garden, with origins in the Kramsacher Loar in the Tyrolean Unterland (eastern part of Tyrol), performed poorly in terms of conservation genetics, with low genetic diversity (number of alleles) and clear genetic differentiation from populations in the wild (high pairwise FST values with wild individuals, clear separation in cluster analysis). Habitat restoration programs are a crucial aspect of amphibian conservation, as they restore ecosystems that are critical to the animals survival. While breeding programs can play an additional role in the future, they must carefully consider genetic diversity to ensure resilient and viable populations, especially in the face of climate change and chytrid fungus infection. This study emphasizes the significance of considering the geographic origin and genetic diversity of newts in conservation efforts. It also serves as a foundation for future population genetic studies of newts in Austria.

molecular biology↗

bioRxiv2025

RNA binding by ADARs prevents RNA interference from attacking self-produced dsRNA

The ability of an organism to identify self and foreign RNA is central to eliciting an immune response in times of need while avoiding autoimmunity. As viral pathogens typically employ double-stranded RNA (dsRNA), host identification, modulation, and response to dsRNA is key. However, dsRNA is also abundant in host transcriptomes, raising the question of how these molecules can be differentiated. Two host pathways that regulate dsRNA are A-to-I RNA editing by adenosine deaminases (ADARs), and RNA interference (RNAi). Both mechanisms are important for normal organism development and function by regulating gene expression. Herein, we studied the structure and amount of siRNAs at editing sites and the ability of ADARs to prevent exogenous RNAi using the model organism, Caenorhabditis elegans. We found that the number of siRNAs targeting edited genes is significantly upregulated in ADAR mutant animals. We also found that despite an almost complete depletion of primary siRNAs generated from editing sites in wildtype animals, secondary siRNAs are generated from edited transcripts, suggesting ADARs antagonize only the first step of RNAi processing. We show that ADARs interfere with the efficacy of exogenous RNAi in vivo, probably to prevent trans-silencing, and have indications that ADR-2 binding to the dsRNA is needed for the efficient prevention of RNAi. This work sheds light on how the RNA editing process protects self-produced dsRNAs from aberrant recognition by the immune processes in the cell and from by-product degradation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/672520v2_ufig1.gif" ALT="Figure 1"> View larger version (72K): org.highwire.dtl.DTLVardef@b34f2corg.highwire.dtl.DTLVardef@130c88org.highwire.dtl.DTLVardef@9be2eborg.highwire.dtl.DTLVardef@4ebeec_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2025

USP15: the fourth Proteasome-associated DUB

The human genome encodes approximately 100 deubiquitinating enzymes (DUBs), but only three are considered proteasome-associated DUBs (pDUBs): PSMD14/Rpn11, USP14, and UCHL5. Among these, only PSMD14 is an integral 19S subunit, whereas USP14 and UCHL5 bind transiently to specific proteasomal subunits. Given the dynamic nature of proteasome composition, we searched for additional pDUBs. USP15 was found to be associated with 26S proteasomes purified from cultured cells. In proteasome preparations from erythrocytes, USP15 was identified as the most abundant transient pDUB. It was even feasible to separate proteasomes containing USP15 from those containing USP14. Although USP15 utilizes an internal ubiquitin-like (UBL) domain for positioning itself at the proteasome, it did not compete with the UBL-containing USP14. USP15 facilitated substrate selection at the proteasome by efficiently disassembling short polyubiquitin (polyUb) chains, while sparing K48-linked tetra-ubiquitin conjugates from deubiquitination. This feature may aid the proteasome in differentiating between substrates to be rescued from those committed to proteolysis. Identification of a fourth pDUB encourages the continued search for additional proteasome-interacting proteins that modulate its substrate specificity in a context-specific manner.

biochemistry↗

bioRxiv2023

The protein phosphorylation landscape in photosystem I of the desert algae Chlorella sp.

O_LIThe phosphorylation of photosystem II (PSII) and its antenna (LHCII) proteins has been extensively studied and its involvement in state transitions and PSII repair is well known. Yet, very little is known about the extent and functions of phosphorylation of photosystem I (PSI) and its antenna (LHCI) proteins. C_LIO_LIHere, two proteomics methods were applied to generate a detailed map of the phosphorylation sites of the PSI-LHCI proteins in Chlorella ohadii cells that were grown under low- or extreme high-light intensities (LL and HL). Furthermore, we analyzed the content of oxidized tryptophans in these cell types to estimate light-induced oxidative damage to PSI-LHCI. C_LIO_LIOur work revealed the phosphorylation of 11 out of 22 PSI-LHCI subunits. The analyses detected extensive phosphorylation of the LHCI subunits lhca6 and lhca7. Other PSI-LHCI subunits were phosphorylated to a lesser extent. Additionally, we show the accumulation of oxidatively damaged tryptophans in the psaD subunit of PSI of HL-grown C. ohadii. C_LIO_LIThe significant phosphorylation of lhca6 and lhca7 suggests a physiological role during photosynthesis, possibly by altering light-harvesting characteristics and binding of other LHCI subunits. Moreover, we show that psaD is susceptible to photodamage while LHCI is protected from ROS under HL. C_LI

plant biology↗

bioRxiv2019

Escape mutations circumvent a tradeoff between resistance to beta-lactams and a beta-lactamase inhibitor

Beta-lactamase inhibitors are increasingly used to counteract microbial resistance to beta-lactam antibiotics mediated by beta-lactamase enzymes. These inhibitors compete with the beta-lactam drug for the same binding site of the beta-lactamase, thereby generating an inherent evolutionary tradeoff: enzyme mutations that increase its activity against the beta-lactam drug also increase its susceptibility towards the inhibitor. It is unclear how common and accessible are mutants that escape this adaptive tradeoff. Here, systematically constructing and phenotyping a deep mutant library of the ampC beta-lactamase gene of Escherichia coli, we identified escape mutations, which even in the presence of the enzyme inhibitor allow growth at beta-lactam concentrations far exceeding the native inhibitory levels of the wildtype strain. Importantly, while such escape mutations appear for combinations of avibactam with some beta-lactam drugs, for other drugs escape phenotypes are completely restricted. Amplicon sequencing of the selected mutant pool identified these escape mutations and showed that they are rare and drug specific. For the combination of avibactam with aztreonam, an escape phenotype was conferred via multiple substitutions in a single conserved amino acid (Tyr 150). In contrast, a different set of mutations showed an escape phenotype for cefepime, and no escape mutants appeared for piperacillin. The differential adaptive potential of ampC to combinations of avibactam and different beta-lactam drugs can help guide drug treatments that are more resilient to evolution of resistance.

microbiology↗