Biology subjects

Rabani, M.

Publications and source records attributed to Rabani, M..

6 recordsLinked to original sources

bioRxiv2026

A molecular circuit integrates environmental cues to coordinate the exit from developmental dormancy

Diapause is a reversible dormancy state that enables organisms to survive extreme environments. In annual killifishes, embryos use diapause to bridge seasonal drought, but how environmental cues are integrated to trigger exit remains unclear. Here, we combine model-based single-embryo transcriptomics with cross-clade small-molecule screening to define the molecular logic of diapause exit. In the African turquoise killifish (Nothobranchius furzeri), high-resolution profiling uncovered a temporal transcriptional cascade, while transcriptomic-clock analysis revealed reduced transcriptional noise during developmental reactivation. Transcriptome-guided drug-enrichment analysis nominated overlapping compounds across two annual killifish clades, leading to a targeted chemical screen that identified shared activators and inhibitors of diapause exit. Functional assays support a model in which HSP90 integrates temperature-dependent cues with steroid-hormone signaling. Together, these findings reveal shared molecular machinery that couples environmental sensing to developmental timing, aligns diapause exit with favorable conditions, and provides a powerful comparative framework for dissecting vertebrate dormancy control.

developmental biology↗

bioRxiv2026

3'UTR-directed control of poly(A) tail dynamics and mRNA stability in vertebrate embryos

Post-transcriptional regulation determines mRNA fate through multiple interconnected layers of control, and is particularly important in early embryos. However, how 3'UTR sequences coordinate these different regulatory layers remains poorly characterized. Here, we develop multi-UTR, a massively parallel reporter assay that simultaneously tracks poly(A) tail lengths, 3' terminal nucleotide additions, and mRNA stabilities for thousands of 3'UTR sequences across early zebrafish embryogenesis. We show that embryos use a combination of global and 3'UTR-encoded regulatory programs to progressively remodel mRNA tails. Using reporters with various initial tail lengths, we find that the embryonic cytoplasm rapidly overrides pre-set poly(A) lengths. As development proceeds, 3'UTRs drive tail length diversity and longer tails become progressively associated with increased stability. Strikingly, this association is affected by productive translation: in non-coding reporters, the tail length-stability relationship inverts, such that shorter poly(A) tails are associated with greater stability. Poly(A) tail remodeling is accompanied by two waves of terminal nucleotide additions, early guanylation and later uridylation, that mark distinct regulatory states. Together, our results uncover how the 3'UTR regulatory code operates across multiple layers of regulation to dynamically shape maternal mRNA fate during embryogenesis, and establish multi-UTR as a general platform for decoding post-transcriptional regulatory programs.

molecular biology↗

bioRxiv2025

A unified analysis of cell-type and trajectory-associated pathways in single-cell data using Phoenix

Single-cell RNA sequencing has transformed our ability to resolve complex cellular heterogeneity within biospecimens at the molecular level. However, identifying which biological pathways accurately reflect distinct cell types or continuous cellular trajectories remains a major challenge. Traditional methods often miss subtle or non-linear pathway activities, limiting biological interpretability and insights. To address this, we develop Phoenix, a pathway analysis framework that leverages random forest models and non-parametric significance testing to evaluate the relevance of functional gene sets for distinguishing between cell-types and organizing cells along pseudotemporal cellular trajectories. Phoenix reveals both up- and downregulated processes, including those shaped by complex non-linear gene interactions, and quantifies their effect sizes. Applied to human and mouse hematopoiesis as well as zebrafish embryogenesis, Phoenix identifies both cell-type-specific and trajectory-associated pathways, spanning housekeeping, developmental, and lineage-specific programs. It outperforms existing tools in capturing cell-type-specific activities of small pathways and reveals greater overlap in pathway activities across species. Ultimately, Phoenix provides a sensitive and interpretable framework for uncovering biologically meaningful pathways and eliciting the interactions between their components in complex single-cell datasets, opening new opportunities to explore dynamic gene regulation across biological systems.

bioinformatics↗

bioRxiv2024

A comparative analysis across species of maternal mRNA regulation in embryos using QUANTA

AbstractThe post-transcriptional regulation of mRNAs greatly impacts gene expression dynamics, but the underlying regulatory kinetics and sequence rules and how they change between organisms remain elusive. Thousands of pre-loaded maternal transcripts are post-transcriptionally regulated within metazoan embryos, making it an ideal system to investigate mRNA regulation. We present QUANTA, a computational strategy to distinguish transcriptionally silent genes and analyze their regulation. QUANTA uses kinetic models to compare total and polyA+ expression patterns, and dissect quantitative rates of mRNA polyadenylation and degradation. QUANTA analysis of maternally provided mRNAs in zebrafish, frog, mouse and human embryos shows that widespread polyadenylation precedes their degradation. Degradation rates are proportional to the developmental pace of organisms and diverge between orthologs. Rates also scale by adjusting developmental pace of zebrafish with external temperature. Finally, we implement a massively parallel reporter assay that is compatible with QUANTA analysis in zebrafish embryos, and analyze the effects of 3UTR sequences on mRNA kinetics. We pinpoint potential regulatory signals in 3UTRs of each organism. These reveal signals to accelerate maternal degradation in fast-developing organisms, while in slow-developing organisms signals enhance mRNA stability. Our work provides a general strategy to quantify post-transcriptional mRNA kinetics and investigate its sequence-based rules.

systems biology↗

bioRxiv2023

Single-cell temporal dynamics reveals the relative contributions of transcription and degradation to cell-type specific gene expression in zebrafish embryos

AbstractDuring embryonic development, pluripotent cells assume specialized identities by adopting particular gene expression profiles. However, systematically dissecting the underlying regulation of mRNA transcription and degradation remains a challenge, especially within whole embryos with diverse cellular identities. Here, we collect temporal cellular transcriptomes of zebrafish embryos, and decompose them into their newly-transcribed (zygotic) and pre-existing (maternal) mRNA components by combining single-cell RNA-Seq and metabolic labeling. We introduce kinetic models capable of quantifying regulatory rates of mRNA transcription and degradation within individual cell types during their specification. These reveal different regulatory rates between thousands of genes, and sometimes between cell types, that shape spatio-temporal expression patterns. Transcription drives most cell-type restricted gene expression. However, selective retention of maternal transcripts helps to define the gene expression profiles of germ cells and enveloping layer cells, two of the earliest specified cell-types. Coordination between transcription and degradation restricts expression of maternal-zygotic genes to specific cell types or times, and allows the emergence of spatio-temporal patterns when overall mRNA levels are held relatively constant. Sequence-based analysis links differences in degradation to specific sequence motifs. Our study reveals mRNA transcription and degradation events that control embryonic gene expression, and provides a quantitative approach to study mRNA regulation during a dynamic spatio-temporal response.

genomics↗

bioRxiv2021

Topic: Hyper immune Bovine Colostrum as a Low-Cost, Large-Scale Source of Antibodies against COVID-19

Many different strategies have been used to fight against COVID-19 pandemic as a therapeutics or prophylaxis approaches. However, none of them so far have used, passive immune transfer using products from immunized farm animals. Hyper immune bovine colostrums (HBC) have been used against many different respiratory and gastrointestinal tracts infections during past decades. Six mixed Holstein X Semental dairy cattles in their 6-7 months of gestation period years were chosen for hyper immunization with COVID-19 vaccine. An isolated and very well protected site was selected and equipped according to animal husbandry code of practice, used for animal experimentation. Specific IgG level against SARS-CoV-2 virus was measured before and after vaccination in the sera, and in the colostrum following parturition. Very high specific IgG level was detected one week following second vaccination in the sera and in first colostrums after parturition. Safety of the product was approved following phase 1 of clinical trials in 40 healthy volunteers. Phase 2 of the clinical trials is underway. Early results show effectiveness of the product in reducing sore throat and cough in early stages of SARS-CoV-2 infection.

microbiology↗