Biology subjects

Singh, D.

Publications and source records attributed to Singh, D..

At least 91 records · Page 5Linked to original sources

bioRxiv2022

Emergent dynamics of underlying regulatory network links EMT and androgen receptor-dependent resistance in prostate cancer

Advanced prostate cancer patients initially respond to hormone therapy, be it in the form of androgen deprivation therapy or second-generation hormone therapies, such as abiraterone acetate or enzalutamide. However, most men with prostate cancer eventually develop hormone therapy resistance. This resistance emerges in several ways, such as through genetic mutations, epigenetic mechanisms, or through non-genetic pathways, such as lineage plasticity along epithelial-mesenchymal or neuroendocrine-like axes. These mechanisms of hormone therapy resistance often co-exist within a single patients tumor and can overlap within a single cell. There exists a growing need to better understand how phenotypic heterogeneity and plasticity results from emergent dynamics of the regulatory networks governing androgen independence. Here, we investigated the dynamics of a regulatory network connecting the drivers of androgen receptor (AR) splice variant-mediated androgen independence and those of epithelial-mesenchymal transition. Model simulations for this network revealed four possible phenotypes: epithelial-sensitive (ES), epithelial-resistant (ER), mesenchymal-resistant (MR) and mesenchymal-sensitive (MS), with the latter phenotype occurring rarely. We observed that well-coordinated "teams" of regulators working antagonistically within the network enable these phenotypes. These model predictions are supported by multiple transcriptomic datasets both at single-cell and bulk levels, including in vitro EMT induction models and clinical samples. Further, our simulations reveal spontaneous stochastic switching between the ES and MR states. Addition of the immune checkpoint molecule, PD-L1, to the network was able to capture the interactions between AR, PD-L1, and the mesenchymal marker SNAIL, which was also confirmed through quantitative experiments. This systems-level understanding of the driver of androgen independence and EMT could aid in understanding non-genetic transitions and progression of such cancers and help in identifying novel therapeutic strategies or targets.

cancer biology↗

bioRxiv2022

A pathogen-induced putative NAC transcription factor mediates leaf rust resistance in barley

Leaf rust, caused by Puccinia hordei, is one of the most widespread and damaging foliar diseases affecting barley (Hordeum spp.). The barley leaf rust resistance locus Rph7, located on the short arm of chromosome 3H, confers defence at all growth stages and was previously shown to have unusually high sequence and haplotype divergence. Earlier, four candidate genes for Rph7 were reported and, despite an in-depth comparative sequence analysis and haplotypic characterisation, the causal gene could not be resolved. Here, we successfully cloned Rph7 utilising a fine mapping approach in combination with an RNA-Seq based expression analysis. We identified three up-regulated and pathogen-induced genes with presence/absence variation (PAV) at this locus. Sequence analysis of chemically induced Rph7 knockout mutant lines identified multiple independent non-synonymous variants, including a premature stop codon in a single non-canonical resistance gene that encodes a 302-amino acid protein. Progeny from four independent transgenic lines segregated for the expected avirulent Rph7 infection type in response to several avirulent P. hordei pathotypes, however, all plants were susceptible to a single virulent pathotype confirming the specificity. Structural analysis using an AlphaFold2 protein model suggests that Rph7 encodes a putative NAC transcription factor, as it shares structural similarity to ANAC019 from Arabidopsis, with a C-terminal BED domain. A global gene expression analysis suggests Rph7 is involved in the activation of basal defence.

genetics↗

bioRxiv2022

Development of the visual system in social poison frog tadpoles

The ways in which animals sense the world changes throughout development. For example, young of many species have limited visual capabilities, but still make social decisions, likely based on information gathered through other sensory modalities. Poison frog tadpoles display complex social behaviors that have been suggested to rely on vision despite a century of research indicating tadpoles have poorly-developed visual systems relative to adults. Alternatively, other sensory modalities, such as the lateral line system, are functional at hatching in frogs and may guide social decisions while other sensory systems mature. Here, we examined development of the mechanosensory lateral line and visual systems in tadpoles of the mimic poison frog (Ranitomeya imitator) that use vibrational begging displays to stimulate egg feeding from their mothers. We found that tadpoles hatch with a fully developed lateral line system. While begging behavior increases with development, ablating the lateral line system inhibited begging in pre-metamorphic tadpoles, but not in metamorphic tadpoles. We also found that the increase in begging and decrease in reliance on the lateral line co-occurs with increased retinal neural activity and gene expression associated with eye development. Using the neural tracer neurobiotin, we found that axonal innervations from the eye to the brain proliferate during metamorphosis, with little retinotectal connections in recently-hatched tadpoles. We then tested visual function in a phototaxis assay and found tadpoles prefer darker environments. The strength of this preference increased with developmental stage, but eyes were not required for this behavior, possibly indicating a role for the pineal gland. Together, these data suggest that tadpoles rely on different sensory modalities for social interactions across development and that the development of sensory systems in socially complex poison frog tadpoles is similar to that of other frog species.

developmental biology↗

bioRxiv2022

Deep Neural Networks Predict MHC-I Epitope Presentation and Transfer Learn Neoepitope Immunogenicity

Identifying neoepitopes that elicit an adaptive immune response is a major bottleneck to developing personalized cancer vaccines. Experimental validation of candidate neoepitopes is extremely resource intensive, and the vast majority of candidates are non-immunogenic, making their identification a needle-in-a-haystack problem. To address this challenge, we present computational methods for predicting MHC-I epitopes and identifying immunogenic neoepitopes with improved precision. The BigMHC method comprises an ensemble of seven pan-allelic deep neural networks trained on peptide-MHC eluted ligand data from mass spectrometry assays and transfer learned on data from assays of antigen-specific immune response. Compared with four state-of-the-art classifiers, BigMHC significantly improves the prediction of epitope presentation on a test set of 45,409 MHC ligands among 900,592 random negatives (AUROC=0.9733, AUPRC=0.8779). After transfer learning on immunogenicity data, BigMHC yields significantly higher precision than seven state-of-the-art models in identifying immunogenic neoepitopes, making BigMHC effective in clinical settings. All data and code are freely available at https://github.com/KarchinLab/bigmhc.

bioinformatics↗

bioRxiv2022

MicroProteins miP1b/BBX30 and miP1a/BBX31 form a positive feedback loop with ABI5 to retard seedling establishment

In plants the switch to autotrophic growth involves germination followed by post-germination seedling establishment. When environmental conditions are not favorable, the stress hormone Abscisic Acid (ABA) signals plants to postpone seedling establishment by inducing the expression of the transcription factor ABI5. The levels of ABI5 determine the efficiency of the ABA mediated post-germination developmental growth arrest. The molecular mechanisms regulating the stability and activity of ABI5 during the transition to light are less known. We found that two microProteins miP1a/ BBX31 and miP1b/BBX30 alongwith ABI5 inhibit post-germination seedling establishment in a partially interdependent manner. MicroProteins are single-domain proteins that interact with multi-domain proteins to modulate their post-translational activity. miP1a/ BBX31 and miP1b/BBX30 physically interact with ABI5 to stabilize it and promote its binding to promoters of downstream genes in light. ABI5 reciprocally induces the expression of BBX30 and BBX31 by directly binding to their promoter. ABI5 and the two microProteins thereby form a positive feedback loop to promote ABA-mediated developmental arrest of seedlings. Our study highlights the functional versatility of microProteins which can act as regulators of crucial developmental transitions in plants as well as other eukaryotes.

plant biology↗

bioRxiv2022

PandoraRL: DQN and Graph Convolution based ligand pose learning for SARS-COV1 Mprotease

The ability to predict the correct ligand binding pose for proteinligand complex is vital for drug design. Recently several machine learning methods have suggested knowledge based scoring functions for binding energy prediction. In this study, we propose a reinforcement learning (RL) based model, PandoraRL, where the RL agent helps the ligand traverse to the optimal binding pose. The underlying representation of molecules utilizes generalized graph convolution to represent the protein ligand complex with various atomic and spatial features. The representation consists of edges formed on the basis of inter molecular interactions such as hydrogen bonds, hydrophobic interactions, etc, and nodes representing atomic features. This study presents our initial model which can train on a protein-ligand pair and predict optimal binding pose for a different ligand with the same protein. To the best of our knowledge, this is the first time an RL based approach has been put forward for predicting optimized ligand pose. CCS CONCEPTSO_LIComputing methodologies [->] Reinforcement learning. C_LI

bioinformatics↗

bioRxiv2022

Transcriptional signature pattern in black, blue and purple wheat and impact on seed pigmentation and other associated features: Comparative transcriptomics, genomics and metabolite profiling

Anthocyanin biosynthesis in plants is complex, especially in a polyploid monocot wheat plant. Using whole-genome sequencing, transcriptomics, and LC-MS/MS, we investigated anthocyanin production in pigmented (black, blue, and purple) wheat seeds. According to differential gene expression profiling, 2AS-MYC, 7DL-MYB, WD40 regulatory genes controls purple pericarp coloration, 4DL-MYC, 2AS-MYC, 7DL-MYB, WD40 controls blue aleurone coloration, and 4DL-MYC, 7DL-MYB, WD40 controls black aleurone colour. We believe that at least one MYC and MYB isoform is sufficient to regulate the anthocyanin synthesis in pericarp or aleurone. Based upon the reduced expressions of the genes belonging to the 4D, SSR molecular marker mapping, variant calling using genome sequencing and IGV browser gene structure visualization, it was inferred that the advanced black and blue wheat lines were substitution lines (4E{4D}), with very small recombinations. Pericarp anthocyanin profiling is controlled by a mutation in chromosome 2AS of purple wheat, and environmental variations more influence pigmented pericarp trait. The expression patterns of anthocyanin structural and other genes varied in different colored wheat, corroborating differences in agronomical metrics.

plant biology↗

bioRxiv2022

Elongated Hypocotyl 5 (HY5) regulates BRUTUS (BTS) to maintain Iron homeostasis in Arabidopsis thaliana.

Iron (Fe) is an essential micronutrient for both plants and animals. Fe limitation significantly reduces crop yield and therefore has adverse impacts on human nutrition. Owing to limited bioavailability of Fe, plants have adapted different strategies that regulate Fe uptake and homeostasis. Particularly, modifications of root growth traits are a key for the survival of plants on Fe-deficient soils. Understanding the molecular basis for these root growth responses will have critical implications for plant breeding. Fe uptake is regulated by a cascade of basic helix-loop-helix (bHLH) transcription factors. In our study, we show that HY5 (Elongated Hypocotyl 5), a member of the basic leucine zipper (bZIP) family of transcription factors plays an important role in the Fe deficiency signalling pathway in Arabidopsis thaliana. The hy5 mutant plants failed to mount an optimum Fe deficiency response and showed severe root growth defects under Fe limitation that could be partially reverted by complementation of hy5 mutant. qRT-PCR analysis revealed that the induction of the genes involved in Fe uptake pathway [FER-like iron deficiency-induced transcription factor (FIT), Ferric Reduction Oxidase 2 (FRO2) and Iron-Regulated Transporter1 (IRT1)] is significantly reduced in the hy5 mutants as compared to the wild-type plants under Fe deficiency. Moreover, we also found that HY5 function is critical for activating the expression of coumarin biosynthesis genes (F6H1, S8H, PDR9 and BGLU42) under Fe deficiency. Interestingly, our results showed that HY5 acts as a negative regulator of BRUTUS (BTS) which is known to negatively regulate Fe deficiency response. Chromatin Immunoprecipitation followed by qPCR revealed direct binding of HY5 to the promoter of BTS. Altogether, our results showed that HY5 plays an important role in regulation of Fe deficiency responses in Arabidopsis.

plant biology↗

bioRxiv2022

Spatiotemporal patterning enabled by gene regulatory networks

Spatiotemporal pattern formation plays a key role in various biological phenomena including embryogenesis and neural network formation. Though the reaction-diffusion systems enabling pattern formation have been studied phenomenonlogically, the biomolecular mechanisms behind these processes has not been modelled in detail. Here, we study the emergence of spatiotemporal patterns due to simple synthetic commonly observed two- and three-node gene regulatory network motifs coupled with their molecular diffusion in one- and two-dimensional space. We investigate the patterns formed due to the coupling of inherent multistable and oscillatory behavior of toggle switch (two mutually repressing nodes), toggle switch with double self-activation, toggle triad (three mutually repressing nodes) and repressilator (three nodes repressing the other sequentially in a cyclic manner) with the effect of spatial diffusion of these molecules. We probe various parameter regimes corresponding to different regions of stability (monostable, multistable, oscillatory) and assess the impact of varying diffusion coefficients too. This analysis offers valuable insights into the design principles of pattern formation facilitated by these network motifs, and suggest mechanistic underpinnings of biological pattern formation.

biophysics↗

bioRxiv2022

Symbolic quantitative cognition in wild zebrafish (Danio rerio)

Zebrafish (Danio rerio) constitute an excellent model system to investigate the neural and genetic basis of quantitative cognition We tested the ability of reward quantity discrimination of wild-type zebrafish in an associative learning task. We used an operant conditioning paradigm in which the number of horizontal lines zebrafish approached in a 2-alternative forced choice task predicted the number of food reward pellets they would receive. Zebrafish did not learn a preference for the 2-line stimulus predictive of receiving 2 food pellets. However, a subset of the fish performed significantly above chance in a discrimination task with the same apparatus, in which the 2-line stimulus was associated with the same reward but the choice of the 1-line stimulus was not rewarded. Zebrafish also showed a population level learning in a simpler spatial association task with the same apparatus. We also explored the explanatory value of alternative spatial learning hypotheses such as a Win-Stay, Lose-Shift (WSLS) strategy at the individual level for fish in navigating these spatially randomised tasks.

animal behavior and cognition↗

bioRxiv2022

Proteochemometric method for pIC50 prediction of Flaviviridae

Viruses remain an area of concern despite constant development of antiviral drugs and therapies. One of the contributors among others is the flaviviridae family of viruses. Like other spaces, antiviral peptides (AVP) are gaining importance for studying flaviviridae family. Along with antiviral properties of peptides, information about bioactivity takes it even closer to accurate predictions of peptide capabilities. Experimental identification of bioactivity of each potential peptide is an expensive and time consuming task. Computational methods like Proteochemometric modelling (PCM) are promising for prediction of bioactivity based on peptide and target sequence. The additional edge PCM methods bring in is the aspect of considering both peptide and target properties instead of only looking at peptide properties. In this study, we propose prediction of pIC50 for AVP against flaviviridae family target proteins. The target proteins were manually curated from literature. Here we utilize the PCM descriptors as peptide descriptors, target descriptors and cross term descriptors. We observe taking peptide and target information improves the results qualitatively and gives better pIC50 predictions. The R2 and MAPE values are 0.85 and 8.44 % respectively

bioinformatics↗

bioRxiv2022

Lhx2 in germ cells suppresses endothelial cell migration in the developing ovary

LIM-homeobox genes play multiple roles in developmental processes, but their roles in gonad development are not completely understood. Herein, we report that Lhx2, Ils2, Lmx1a, and Lmx1b are expressed in a sexually dimorphic manner in mouse, rat, and human gonads during sex determination. Amongst these, Lhx2 has female biased expression in the developing gonads of species with environmental and genetic modes of sex determination. Single-cell RNAseq analysis revealed that Lhx2 is exclusively expressed in the germ cells of the developing mouse ovaries. To elucidate the roles of Lhx2 in the germ cells, we analyzed the phenotypes of Lhx2 knockout XX gonads. While the gonads developed appropriately in Lhx2 knockout mice and the somatic cells were correctly specified in the developing ovaries, transcriptome analysis revealed enrichment of genes in the angiogenesis pathway. There was an elevated expression of several pro-angiogenic factors in the Lhx2 knockout ovaries. The elevated expression of pro-angiogenic factors was associated with an increase in numbers of endothelial cells in the Lhx2-/-ovaries at E13.5. Gonad recombination assays revealed that the increased numbers of endothelial cells in the XX gonads in absence of Lhx2 was due to ectopic migration of endothelial cells in a cell non-autonomous manner. We also found that, there was increased expression of several endothelial cell-enriched male-biased genes in Lhx2 knockout ovaries. Also, in absence of Lhx2, the migrated endothelial cells formed an angiogenic network similar to that of the wild type testis, although the coelomic blood vessel did not form. Together, our results suggest that Lhx2 in the germ cells is required to suppress vascularization in the developing ovary. These results suggest a need to explore the roles of germ cells in the control of vascularization in developing gonads. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/483280v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@59ca47org.highwire.dtl.DTLVardef@ef193eorg.highwire.dtl.DTLVardef@162651corg.highwire.dtl.DTLVardef@dc3d0f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightO_LIMultiple LIM-HD genes are expressed in developing gonads during the window of sex determination with Lhx2 having female dominating expression in an evolutionarily conserved manner C_LIO_LILhx2 is expressed in the germ cells of developing mouse ovaries C_LIO_LILoss of Lhx2 in the developing ovaries alters the expression of genes involved in various pathways including angiogenesis C_LIO_LILhx2 in germ cells suppress endothelial cell migration in the developing ovaries C_LI

developmental biology↗

bioRxiv2022

A model of autonomous interactions between hippocampus and neocortex driving sleep-dependent memory consolidation

How do we build up our knowledge of the world over time? Many theories of memory formation and consolidation have posited that the hippocampus stores new information, then "teaches" this information to neocortex over time, especially during sleep. But it is unclear, mechanistically, how this actually works -- how are these systems able to interact during periods with virtually no environmental input to accomplish useful learning and shifts in representation? We provide a framework for thinking about this question, with neural network model simulations serving as demonstrations. The model contains hippocampus and neocortical areas, which replay memories and interact with one another completely autonomously during simulated sleep. Oscillations are leveraged to support error-driven learning that leads to useful changes in memory representation and behavior. The model has a non-Rapid Eye Movement (NREM) sleep stage, where dynamics between hippocampus and neocortex are tightly coupled, with hippocampus helping neocortex to reinstate high-fidelity versions of new attractors, and a REM sleep stage, where neocortex is able to more freely explore existing attractors. We find that alternating between NREM and REM sleep stages, which alternately focuses the models replay on recent and remote information, facilitates graceful continual learning. We thus provide an account of how the hippocampus and neocortex can interact without any external input during sleep to drive useful new cortical learning and to protect old knowledge as new information is integrated.

neuroscience↗

bioRxiv2022

Tobacco HY5, NtHY5, positively regulates flavonoid biosynthesis and enhances salt stress tolerance

Tobacco remains one of the most commercially important crops due to the parasympathomimetic alkaloid nicotine used in cigarettes. Most genes involved in nicotine biosynthesis are expressed in root tissues; however, their light-dependent regulation has not been studied. We identified the ELONGATED HYPOCOTYL 5 homolog, NtHY5, from Nicotiana tabacum and demonstrated its role in nicotine biosynthesis. We report the development of CRISPR/Cas9-based mutant plants, NtHY5CR, and show down-regulation of the nicotine biosynthetic pathway, whereas NtHY5 overexpression (NtHY5OX) plants show the opposite effect. Grafting experiments using wild type, NtHY5CR, and NtHY5OX indicated that NtHY5 moves from shoot-to-root to regulate nicotine biosynthesis in the root tissue. We conclude that shoot HY5, directly or through enhancing expression of the HY5 in the root, promotes nicotine biosynthesis. The CRISPR/Cas9-based mutants developed, in this study; with low nicotine accumulation in leaves could help people to overcome their nicotine addiction and the risk of death from tobacco use.

plant biology↗

bioRxiv2021

Emergence of planar cell polarity from the interplay of asymmetric interaction and tissue-level gradients

Planar cell polarity (PCP) - tissue-scale alignment of the direction of asymmetric localization of proteins at cell-cell interface - is essential for embryonic development and physiological functions. Abnormalities in PCP can lead to neural tube closure defects and misaligned hair follicles. Decoding the mechanism responsible for PCP establishment and maintenance remains a fundamental open question. While the roles of various molecules - broadly classified into "global" and "local" modules - have been well-studied, their necessity and sufficiency in explaining PCP and connecting their perturbations to experimentally observed patterns has not been examined. Here, we develop a minimal model that captures the proposed features of these modules - a global tissue-level gradient and local asymmetric distribution of protein complexes. Our model suggests that while polarity can emerge without a gradient, the gradient can provide the direction of polarity and maintain PCP robustly in presence of stochastic perturbations. We also recapitulated swirling patterns seen experimentally and features of domineering non-autonomy, using only three free model parameters - protein binding rate, concentration of proteins forming heterodimer across cell boundaries and gradient steepness. We explain how self-stabilizing asymmetric localizations in presence of tissue-level gradient can lead to robust PCP patterns and reveal minimal design principles for a polarized system.

systems biology↗

bioRxiv2021

Continuum Theory for Planar Cell Polarity

Planar Cell Polarity (PCP), characterized by asymmetric localization of proteins at the cell membrane within the epithelial plane, plays essential roles in embryonic development and physiological functions. The significance of PCP can be appreciated by the outcomes of its failure in the form of defects in neural tube formation, tracheal malfunctions, organ shape misregulation, hair follicle misalignment etc. Extensive experimental works on PCP in fruit fly Drosophila melanogaster have classified the proteins involved in PCP into a core module, acting locally by inter-cellular protein interactions, and a global module, responsible for the alignment of cell polarities with that of the tissue axis. Despite the involvement of different molecular players the asymmetric localization of the proteins of the two modules on cell membrane primarily involves inter-cellular dimer formations. We have developed a continuum model of the localization of PCP proteins on the cell membrane and its regulation via intra- and inter-cellular protein-protein interactions. We have identified the conditions for the asymmetric protein localization, or PCP establishment, for uniform and graded protein expression levels in the tissue. We have found that in the absence of any tissue level expression gradient polarized state of the tissue does not arise. However, in the presence of tissue-level expression gradients of proteins the polarized state remains stable. We have also looked at the influence of the loss of PCP proteins from a select region of the tissue on the polarization of the cells outside of that region. This continuum theory of planar cell polarity can be coupled with active-matter hydrodynamics to study cell flows and their regulation by genetic machinery.

biophysics↗

bioRxiv2021

Lattice-based microenvironmental uncertainty driven phenotypic decision-making: a comparison with Notch-Delta-Jagged signaling

Phenotypic decision-making is a process of determining important phenotypes in accordance with the available microenvironmental information. Although phenotypic decision at the level of a single cell has been precisely studied, but the knowledge is still imperceptible at the multicellular level. How cells sense their environment and adapt? How single cells change their phenotype in a multicellular complex environment (without knowing the interactions among the cells), is still a rheotorical question. To unravel the fragmental story of multicellular decision-making, Least microEnvironmental Uncertainty Principle (LEUP) was refined and applied in this context. To address this set of questions, we use variational principle to grasp the role of sensitivity, build a LEUP driven agent-based model on a lattice which solely hinges on microenvironmental information and investigate the parallels in a well-known biological system, viz., Notch-Delta-Jagged signaling pathway. The analyses of this model led us to interesting spatiotemporal patterns in a population of cells, responsive to the sensitivity parameter and the radius of interaction. This resembles the tissue-level pattern of a population of cells interacting via Notch-Delta-Jagged signaling pathway in some parameter regimes.

biophysics↗

bioRxiv2021

Identification of mRNAs that undergo stop codon readthrough in Arabidopsis thaliana

A stop codon ensures termination of translation at a specific position on an mRNA. Sometimes, termination fails as translation machinery recognizes a stop codon as a sense codon. This leads to stop codon readthrough (SCR) resulting in the continuation of translation beyond the stop codon, generating protein isoforms with C-terminal extension. SCR has been observed in viruses, fungi, and multicellular organisms including mammals. However, SCR is largely unexplored in plants. In this study, we have analyzed ribosome profiling datasets to identify mRNAs that undergo SCR in Arabidopsis thaliana. Analyses of the ribosome density, ribosome coverage and three-nucleotide periodicity of the ribosome profiling reads, in the mRNA region downstream of the stop codon, provided strong evidence for SCR in mRNAs of 144 genes. This process generates putative peroxisomal targeting signal, nuclear localization signal, prenylation signal, transmembrane helix and intrinsically disordered regions in the C-terminal extension of several of these proteins. Gene ontology (GO) functional enrichment analysis revealed that these 144 genes belong to three major functional groups - translation, photosynthesis and abiotic stress tolerance. Finally, using a luminescence-based assay, we experimentally demonstrate SCR in representative mRNAs belonging to these functional classes. Based on these observations, we propose that SCR plays an important role in plant physiology by regulating the protein localization and function. AUTHOR SUMMARYProtein synthesis executed by macromolecular complexes, termed ribosomes, starts and stops at specific locations on a messenger RNA (mRNA). This fidelity is critical for the normal functioning of cells. However, sometimes ribosomes dont stop translation at the stop signal (termed stop codon) on an mRNA resulting in longer proteins with properties different from those of the canonical shorter protein. This process called stop codon readthrough (SCR) has been observed in viruses, fungi, and multicellular organisms including mammals. However, it remains largely unexplored in plants. In this study, we report evidence of SCR in 144 genes of Arabidopsis thaliana, a small flowering weed widely used as a model system to study plant biology. These genes are involved in protein synthesis, photosynthesis and stress tolerance in plants. We have also experimentally demonstrated SCR in a few genes that represent these functional classes. Our analysis shows that SCR can change the localization and functional properties of these proteins. We propose that SCR plays an important role in plant physiology.

plant biology↗