Biology subjects

Joshi, D. C.

Publications and source records attributed to Joshi, D. C..

5 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

A Novel Mechanism for Tauopathy in Progressive Multiple Sclerosis: Excitotoxic Misplacement of a Mitochondrial Anchor into Dendrites Driven by Tau-hyperphosphorylation

On April 2nd, 2025, the FDA approved a Fast Track Designation for Biogen to use Antisense Oligonucleotides (ASO) to treat tauopathy in clinical trials for Alzheimers Disease (AD) to meet an unmet medical need [1]. For Multiple Sclerosis (MS), there is a similar unmet medical need regarding tauopathy when MS transitions into the late, or Progressive MS that is currently incurable. AD and MS share commonality: there is comorbidity between AD and MS [2], and the recent awareness that progressive MS may be considered a secondary tauopathy [3]. This study lays the basic science foundation for a future repurposing of ASO tauopathy therapy from AD to MS. The central hypothesis is that in Progressive MS, tauopathy is not a passive bystander but an active contributor to synaptic degeneration through a novel toxic target known as DSI (Dendritic Syntaphilin Intrusion) discovered in our laboratory. In this hypothesis, the excitotoxic N-methyl-D-aspartate receptor (NMDAR) GluN2B activates Tau hyperphosphorylation (p-Tau), leading to the mislocalization or intrusion of a mitochondrial anchor SNPH into neuronal dendrites (DSI). This causes mitochondrial damage and subsequent synapse/dendrite disintegration. In support of this hypothesis that tauopathy is a key driver of DSI, we demonstrated using primary neuronal cultures that inhibitors of p-Tau kinases and Tau-KO both completely abolish DSI. We propose that a therapy for Progressive MS is repurpose the existing FDA-approved ASO Tau knockdown therapy from AD to treat MS. FundingNIH R01 MSN233781 to SY Chiu

neuroscience↗

bioRxiv2025

A comprehensive analysis of the inherited lncRNA and circRNA repertoire of zebrafish

Inherited non-coding RNAs can be the third major component of epigenetic information transfer from one generation to the next. Here, we present a comprehensive resource of lncRNAs and circular RNAs that are inherited, compiled from meta-analysis of zebrafish transcriptomics data and comparative genomics with mouse and human. Maternal and paternal inheritance of mRNA into the zygote is accepted to be an important regulator of embryonic development as well as adult characteristics. Although inheritance of certain specific miRNAs is known, other non-coding RNA inheritance remains less explored. We performed a comprehensive analysis of the inherited lncRNAs and circRNAs in zebrafish. We discovered that nearly 20% of all known lncRNA and 7% of circRNAs are inherited. Many of these lncRNAs are conserved in mammals, and are expressed widely in adult tissues of zebrafish. The male and female gametes carry a highly similar pool of inherited lncRNAs, with only a few sperm/ oocyte specific transcripts. The majority of inherited circRNAs originate from genes important for fertilization and can potentially regulate translational processes. Contrary to general belief, the inherited lncRNAs and circRNAs do not undergo degradation en masse coincidental to zygotic genomic activation, suggesting that these RNAs may have more sustained roles in development.

bioinformatics↗

bioRxiv2023

An associative transcriptomics study on rice bean (Vigna umbellata) provides new insights into genetic basis and candidate genes governing flowering, maturity and seed weight

Rice bean is an underrated legume with significant potential to support food and nutritional security worldwide, being a rich source of proteins, minerals, and essential fatty acids. Therefore, we considered three pivotal production traits of rice bean; flowering, maturity and seed weight, to identify associated candidate genes. One-hundred diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank were considered for phenotypic data collection and genotyping by transcriptome sequencing approach. Association analysis involving various GWAS models was conducted to identify significant marker-trait associations. The results revealed association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The annotation of associated transcripts unraveled the functional genes related to the considered traits. Among the significant candidate genes identified, HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A were found associated with flowering. Further, associations of WRKY1 and DEAD-box-RH27 with seed weight, PIF3 and pentatricopeptide-repeat-containing-gene with maturity & seed weight and aldo-keto-reductase with flowering & maturity have been revealed. The present investigation provides insights into the genetic mechanisms governing economically-essential traits like flowering, maturity and seed weight that can be potentially utilized for rice bean improvement. HighlightsThe present investigation is the first associative transcriptomics approach implemented on Vigna umbellata. Based on the marker-trait association analysis, candidate genes for flowering, maturity and seed weight traits are reported.

bioinformatics↗

bioRxiv2023

SMIM36, a novel and conserved microprotein, is involved in retinal lamination in zebrafish.

Microproteins are small proteins comprising 2 to 200 amino acids, arising from small Open Reading Frames (smORFs). They are found in different parts of the cell and regulate basic molecular processes like DNA replication, repair, transcription and recombination. SMIM or SMall Integral Membrane proteins are novel, largely uncharacterized, members to the class of microproteins defined by the presence of a transmembrane domain. The retinal transcriptome of zebrafish, reported previously by our group, revealed several novel mRNA transcripts that show oscillating expression in a diurnal manner. Here, we show that one of these transcripts encodes the zebrafish homolog of the human SMIM36 protein, which has not been functionally characterised. This highly conserved microprotein is expressed in the human and zebrafish retina, and efficiently translated in cell lines. Using single-cell RNA-seq datasets, we found that it is expressed in the bipolar cells, rods and Muller glia in the human retina. The knockdown of SMIM36 using splice-block morpholino caused microphthalmia and defects in the retinal layers in zebrafish. Therefore, we show the role of a microprotein in the neural retina thus paving the way for future studies on the role of SMIM proteins in retinal disorders.

developmental biology↗