Biology subjects

Chaturvedi, G.

Publications and source records attributed to Chaturvedi, G..

3 recordsLinked to original sources

bioRxiv2024

A prion-like protein regulates the 2-dimensional to 3-dimensional growth transition in the moss Physcomitrium patens

The colonization of the land by plants coincided with the evolution of 3-dimensional (3D) growth; the acquisition of apical cells with the capacity to rotate the plane of cell division. The moss Physcomitrium patens has recently been developed as a model to dissect the genetic basis of 3D growth, an invariable and unifying feature of all land plants. The cytokinin-unresponsive Ppnog1-R mutant incorrectly orients division planes in developing buds and thus fails to make the transition to 3D growth. To reveal the genetic interactors of the PpNOG1 gene, which encodes a protein with a C-terminal UBA domain, we performed a screen and identified the suppressor of nog1a (snog1a) mutant. We have mapped the causative mutation to a gene that encodes a prion-like protein related to FLOE2/3 and demonstrated that the mutant phenotypes observed in both a nog1 disruptant mutant (nog1dis) and snog1a can be attributed to changes in cytokinin perception. We present a revised model for 3D growth and suggest that the 2D-to-3D growth transition is regulated, at least in part, by liquid-liquid phase separation (LLPS). SUMMARY STATEMENTThe transition to 3D growth is negatively regulated by a prion-like protein that both alters cytokinin signaling and has been implicated in liquid-liquid phase separation (LLPS).

plant biology↗

bioRxiv2020

Genetic differences between extreme and composite constitution types from whole exome sequences reveal actionable variations

Personalized medicine relies on successful identification of genome-wide variations that governs inter-individual differences in phenotypes and system level outcomes. In Ayurveda, assessment of composite constitution types "Prakriti" forms the basis for risk stratification, predicting health and disease trajectories and personalized recommendations. Here, we report a novel method for identifying pleiotropic genes and variants that associate with healthy individuals of three extreme and contrasting "Prakriti" constitutions through exome sequencing and state-of-the-art computational methods. Exome Seq of three extreme Prakriti types from 108 healthy individuals 54 each from genetically homogeneous populations of North India (NI, Discovery cohort) and Western India (VADU, Replication cohort) were evaluated. Fishers Exact Test was applied between Prakriti types in both cohorts and further permutation based p-value was used for selection of exonic variants. To investigate the effect of sample size per genetic association test, we performed power analysis. Functional impact of differentiating genes and variations were inferred using diverse resources -Toppfun, GTEx, GWAS, PheWAS, UK Biobank and mouse knockdown/knockout phenotype (MGI). We also applied supervised machine learning approach to evaluate the association of exonic variants with multisystem phenotypes of Prakriti. Our targeted investigation into exome sequencing from NI (discovery) and VADU (validation) cohorts datasets provide ~7,000 differentiating SNPs. Closer inspection further identified a subset of SNPs (2407 (NI) and 2393 (VADU)), that mapped to an overlapping set of 1181 genes. This set can robustly stratify the Prakriti groups into three distinct clusters with distinct gene ontological (GO) enrichments. Functional analysis further strengthens the potential pleiotropic effects of these differentiating genes/variants and multisystem phenotypic consequences. Replicated SNPs map to some very prominent genes like FIG4, EDNRA, ANKLE1, BCKDHA, ATP5SL, EXOCS5, IFIT5, ZNF502, PNPLA3 and IL6R. Lastly, multivariate analysis using random forest uncovered rs7244213 within urea transporter SLC14A2, that associate with an ensemble of features linked to distinct constitutions. Our results reinforce the concept of integration of Prakriti based deep phenotypes for risk stratification of healthy individuals and provides markers for early actionable interventions.

genomics↗

bioRxiv2019

Origin of a novel CYP20A1 lncRNA through 23 Alu exaptations in the human lineage creates a potential multi-miRNA sponge

BackgroundPrimate-specific Alus contribute to transcriptional novelties in conserved gene regulatory networks. Alu RNAs are present at elevated levels in stress conditions and consequently leads to transcript isoform specific functional role modulating the physiological outcome. One of the possible mechanisms could be Alu nucleated mRNA-miRNA interplay. ResultUsing combination of bioinformatics and experiments, we report a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) through exaptation of 23 Alus in its 9kb 3UTR. CYP20A1_Alu-LT, confirmed by 3RACE, is an outlier in length and expressed in multiple cell lines. We demonstrate its presence in single nucleus RNA-seq of [~]16000 human cortical neurons (including rosehip neurons). Its expression is restricted to the higher primates. Most strikingly, miRanda predicts [~]4700 miRNA recognition elements (MREs; with threshold< -25kcal/mol) for [~]1000 miRNAs, which have majorly originated within the 3UTR-Alus post exaptation. We hypothesized that differential expression of this transcript could modulate mRNA-miRNA networks and tested it in primary human neurons where CYP20A1_Alu-LT is downregulated during heat shock response and upregulated upon HIV1-Tat treatment. CYP20A1_Alu-LT could possibly function as a miRNA sponge as it exhibits features of a sponge RNA such as cytosolic localization and [≥]10 MREs for 140 miRNAs. Small RNA-seq revealed expression of nine miRNAs that can potentially be sponged by CYP20A1_Alu-LT in neurons. Additionally, CYP20A1_Alu-LT expression was positively correlated (low in heat shock and high in Tat) with 380 differentially expressed genes that contain cognate MREs for these nine miRNAs. This set is enriched in genes involved in neuronal development and hemostasis pathways. ConclusionWe demonstrate a potential role for CYP20A1_Alu-LT as miRNA sponge through preferential presence of MREs within Alus in a transcript isoform specific manner. This highlights a novel component of Alu-miRNA mediated transcriptional modulation leading to physiological homeostasis.

evolutionary biology↗