Biology subjects

Dayal, S.

Publications and source records attributed to Dayal, S..

3 recordsLinked to original sources

bioRxiv2026

Enhancer RNA like function of intergenic inherited lncRNAs during maternal to zygotic transition in zebrafish

The maternal-to-zygotic transition (MZT) is a major developmental event during which inherited transcripts are remodeled and zygotic transcription is established. Although parentally inherited long noncoding RNAs (lncRNAs) are present in early embryos, they have been thought to be dispensable. We have identified more than 2000 inherited lncRNAs in zebrafish embryos, but how these RNAs participate in regulatory programs during early development has remained unexplored. Here, the inheritance of selected zebrafish lncRNAs spanning a broad expression range were confirmed at the pre-MZT stage and full-length sequences were captured by Direct RNA nanopore sequencing. We show that 30% inherited intergenic lncRNAs are preferentially associated with active enhancers, annotated as such in DANIO CODE, whereas non-inherited intergenic lncRNAs rarely overlap with enhancers. Perturbation of five inherited intergenic lncRNAs, individually, using antisense oligonucleotides reduced the expression of their respective neighboring genes at 2.5, 4.3, and/or 6 hours post fertilization, indicating that these RNAs act as positive local regulators during MZT. Together, these findings identify inherited intergenic lncRNAs as enhancer-associated regulators with elncRNA-like properties during early embryogenesis.

developmental biology↗

bioRxiv2025

Petri Net-Based Framework for Oxygen-Sensitive Regulation of Pyruvate Metabolism in M. tuberculosis

Pyruvate serves as a central hub of cellular metabolism, linking glycolysis with downstream pathways such as the tricarboxylic acid (TCA) cycle, gluconeogenesis, and fermentation. Its metabolic flexibility enables organisms to switch between oxidative and fermentative fates depending on oxygen availability and environmental stress. In this study, a Petri net (PN) model of pyruvate metabolism in Mycobacterium tuberculosis H37Rv was developed to capture and simulate these dynamic transitions. Using Snoopy 2.0 for model construction and COPASI for simulation, the framework incorporated key metabolites, cofactors, and enzymatic processes regulating aerobic and anaerobic states. The model demonstrated that oxygen availability acts as a regulatory switch, channeling pyruvate either toward acetyl-CoA for ATP generation under aerobic conditions or toward lactate production under hypoxia to regenerate NAD+. Structural validation confirmed boundedness, conservativeness, and deadlock-free behavior, underscoring the robustness of the framework. Sensitivity analyses highlighted enzymatic kinetics as critical determinants of flux distribution and system stability. Collectively, the PN model provides a scalable and biologically relevant computational framework for exploring oxygen-dependent metabolic reprogramming, offering insights into energy adaptation and potential therapeutic targets in pathogenic systems.

bioinformatics↗

bioRxiv2023

Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition

The glioblastoma microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine is elevated in the glioblastoma tumor microenvironment. Exogenous administration of spermidine drives tumor aggressiveness in an immune-dependent manner in pre-clinical mouse models via reduction of CD8+ T cell frequency and phenotype. Knockdown of ornithine decarboxylase, the rate-limiting enzyme in spermidine synthesis, did not impact cancer cell growth in vitro but did result in extended survival. Furthermore, glioblastoma patients with a more favorable outcome had a significant reduction in spermidine compared to patients with a poor prognosis. Our results demonstrate that spermidine functions as a cancer cell-derived metabolite that drives tumor progression by reducing CD8+T cell number and function.

cancer biology↗