Magateshvaren Saras, M. A. | bioRxiv Science

bioRxiv2026

Tracing the regulatory atlas of non-coding RNA in human labour

The early onset of labour increases mortality and developmental risks for a human newborn. Key genes in human labour have been investigated using multiple modalities, but their regulation by non-coding RNA (e.g. lncRNA and miRNA) remains incomplete. This study explores the three-way relationship between labour-associated transcription factors (TFs), miRNA and lncRNA suggested by the competing endogenous RNA (ceRNA) hypothesis, to understand the underlying regulatory framework. Experimentally validated miRNA-lncRNA interactions are modelled using five distinct machine learning (ML) architectures to predict 20469 labour-linked miRNA-lncRNA interactions. Known mRNA-ncRNA interactions from databases were included to construct a tripartite network, and a subset of 9989 labour-linked network motifs containing TFs were isolated and analysed. Gene enrichment of nodes in TF-lncRNA-miRNA network, as well as validation from public myometrial datasets indicate high significance in contractile pathways including immune signalling. Experimentally unconfirmed tripartite network motifs have been found, and we elaborate on their potential regulation in labour using 8 TF-lncRNA-miRNA network motifs. A unified ncRNA-TF regulatory atlas in labour has been synthesized, and a complete summary of the tripartite network motifs can be accessed and visualised using the user-friendly, public database.

bioinformatics↗

bioRxiv2025

A genetic signature of resistance to activity-based anorexia in striatal projecting cortical neurons

ObjectiveConverging evidence from neuroimaging studies and genome-wide association study (GWAS) suggests the involvement of prefrontal cortex (PFC) and striatum dysfunction in the pathophysiology of anorexia nervosa (AN). However, identifying the causal role of circuit-specific genes in the development of AN-like phenotype remains challenging and requires the combination of novel molecular tools and preclinical models. MethodsWe used the activity-based anorexia (ABA) rat model in combination with a novel viral-based translating ribosome affinity purification (TRAP) technique to identify transcriptional differences within a specific neural pathway that we have previously demonstrated to mediate pathological weight loss in ABA rats (i.e. medial prefrontal cortex neurons that project to the nucleus accumbens shell). We compared actively transcribed genes in rats susceptible to weight loss to the subpopulation of rats resistant to weight loss under the same experimental conditions. ResultsWe reveal 1424 differentially expressed genes between Susceptible and Resistant rats, highlighting important transcriptional changes associated with ABA within this pathway. The changes observed were independent of current calorie deficit and associated with metabolic, mitochondrial and neural functions. Further, we show that genes upregulated in Resistant rats were involved in mitochondrial function, while downregulated genes were associated with cytoskeletal, postsynaptic and axonal functions, supporting the hypothesis that hyperexcitability of cortico-striatal circuit function is a critical mediator of pathological weight loss in ABA. DiscussionThese findings represent an essential first step in understanding how circuit-specific gene expression patterns may contribute to susceptibility to ABA and provide potential molecular targets for manipulation in this animal model of AN. Public SignificanceThis study identifies specific brain gene activity patterns that may explain why some individuals are more vulnerable to extreme weight loss, as seen in anorexia nervosa. Using an advanced molecular technique in a well-established animal model, key differences in a neural pathway linked to cognitive control were observed. These findings pave the way for more targeted treatments that could prevent or reverse this dangerous condition. SummaryO_LITranscriptional differences within medial prefrontal cortex to nucleus accumbens shell (mPFC-AcbSh) neurons distinguish rats highly susceptible to activity-based anorexia (ABA) from those resistant to pathological weight loss. C_LIO_LIResistant rats showed upregulation of mitochondrial function genes, while Susceptible rats had upregulation of genes related to synaptic structure and signalling, implicating excitability of this circuit in driving maladaptive weight loss behaviour. C_LIO_LITranscriptomic changes align with human genome-wide association study (GWAS) findings and support links between anorexia nervosa and both metabolic and psychiatric comorbidities. C_LIO_LIThe study highlights potential molecular targets for future gene manipulation and therapeutic intervention. It also provides a foundation for creating refined genetic animal models that integrate multiple AN-associated variants to better reflect the polygenic nature of the disorder. C_LI

neuroscience↗

bioRxiv2024

NuCDB: A databank of nucleic acids circular dichroism spectra

Nucleic acids take a variety of secondary structures depending on the sequence and environmental conditions. Circular dichroism (CD) spectroscopy quickly provides the secondary structural information of nucleic acids. Nucleic acid Circular-dichroism DataBank (NuCDB) https://project.iith.ac.in/nucdb/, a repository of nucleic acid secondary structure CD spectra published during 1964-2012, is created. Besides acting as the repository for the nucleic acids CD spectra, NuCDB also has the facility to upload recently published CD spectra to keep the repository up-to-date. This repository provides the sequence-structure-environmental relationship of different nucleic acid fragments in one platform. Until today, CD is used for studying the secondary structure of smaller nucleic acid fragments. Since different parts of the genome and transcriptome of an organism have combinations of various secondary structures and play a crucial role in regulating the biological processes, the CD spectra of longer nucleic acid sequences would be more realistic. Thus, this bioinformatics repository would be helpful in training machine learning models to predict the presence of multiple secondary structures in a given CD spectra.

bioinformatics↗