Biology subjects

Rani, R.

Publications and source records attributed to Rani, R..

15 recordsLinked to original sources

bioRxiv2026

Hematogenous neuroinvasion and genotype-dependent transmission of influenza A H5N1 viruses in the cat host

The spillover of highly pathogenic avian influenza (HPAI) A H5N1 virus to mammalian hosts raises major concerns due to its pandemic potential. Cats are frequently affected mammals, often succumbing to systemic and neurological disease. Here, we characterized the pathogenesis and transmissibility of two H5N1 genotypes, B3.13 and D1.1, in cats. Infected cats exhibited high-level viremia and virus shedding in nasal, oral, and fecal secretions were consistently detected. The virus replicated initially in the upper respiratory tract and lungs, followed by systemic dissemination and neuroinvasion. Notably, the virus crossed the blood-brain-barrier by infecting endothelial cells, spreading to astrocytes and neurons, causing multifocal encephalitis. D1.1-virus infection caused protracted disease with lower shedding and no transmissibility, whereas B3.13 virus caused rapid onset with efficient shedding and transmission. These findings reveal critical H5N1 neuropathogenesis mechanisms and highlight mammalian transmission potential in a species with close human contact.

microbiology↗

bioRxiv2026

Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models

Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models. Using reverse genetics, we rescued three naturally occurring viruses: rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics, replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo. All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited significantly smaller plaques in bovine and human cells. In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared to the other strains. Similarly, as in the mouse experiments, in hamsters, all viruses induced body weight loss and oral shedding, with robust virus replication observed in tissues, but the rMichigan/90 virus presented reduced replication and shedding. Contact transmission studies in hamsters revealed limited transmissibility for these viruses, with only one out of four animals inoculated with the rMichigan/90 virus transmitting it to a naive contact. These findings indicate that both bovine- and human-derived H5N1 genotype B3.13 viruses present high pathogenicity in mammals, though the overall transmissibility remains low. Significance StatementInfluenza A H5N1 virus spilled over from wild birds into dairy cattle in the US in 2024. Since then, an increased number of human infections - with at least 71 confirmed cases - were confirmed. In the present study we evaluated and compared the pathogenicity and transmissibility of a bovine and two human H5N1 viruses of the genotype B3.13. Our results show that while all viruses are pathogenic in mouse and hamster models, the bovine isolate TX2/24 presents a broader tissue tropism than the human derived viruses. Contact transmission studies revealed a limited ability of these viruses to transmit in the hamster contact transmission model. These findings highlight the high pathogenicity of H5N1 viruses in mammals and demonstrate that that their transmissibility potential remains low.

microbiology↗

bioRxiv2025

Integrative comparative transcriptomics using cultivated and wild rice reveals key regulators of developmental and photosynthetic progression along the rice leaf developmental gradient

A comprehensive understanding of gene regulatory networks and the key regulators underlying developmental and physiological progression along the leaf developmental gradient is crucial for optimizing photosynthetic competence. Comparisons of developmental and photosynthetic features across successive leaf developmental stages revealed pronounced differences between wild rice (Oryza australiensis) and three cultivated rice accessions. Global gene expression profiling identified three major transcriptional phases across leaf stages: a predominance of developmental genes at SAM+Pi (initiating primordia) and P3; genes for photosynthetic transition at P3 and P4; and enriched core photosynthetic genes at P4 and P5. O. australiensis showed a more prominent expression of developmental and photosynthetic genes than cultivated accessions across leaf stages. Multivariate analysis further supported a distinct transcriptional landscape in O. australiensis compared with cultivated accessions. Integration of gene expression with species-specific variations in regulatory sequences, derived from synteny-anchored orthology analysis, generated stage-resolved gene regulatory networks and identified key transcription factors (TFs) mediating the developmental and physiological progression. A cross-species comparison of TF-target regulatory networks revealed extensive stage- and accession-dependent rewiring of the regulatory networks of key TFs, with strong regulatory divergence in O. australiensis. Gene silencing of two candidate TFs, OsDOF8 and OsARID2, altered the rice photosynthetic competence with accession-specific effects. Taken together, the study highlights promoter-driven regulatory divergence as a potential mechanism underlying developmental and photosynthetic differences among the rice accessions. The resource is available through an interactive public database, Rice DEV-LEAF (https://nipgr.ac.in/DEV-LEAF/), enabling exploration of gene expression dynamics and regulatory networks across the rice leaf developmental gradient.

plant biology↗

bioRxiv2025

A Platinum Butterfly Effect: Small Changes Turn an Anticancer Drug into a Non-toxic Metalloantibiotic with In Vivo Efficacy

Widespread resistance to all clinically used antibiotics has sparked investigations into alternative sources for novel and effective antimicrobial agents. Metal-based compounds (metalloantibiotics) have emerged as a promising class of potential antibiotics exhibiting high hit rates against critical bacterial pathogens while not displaying higher toxicity than organic compounds. Here, we describe the exploration of a novel class of non-toxic, Gram-positive acting platinum-based antibacterial agents with micro to nanomolar activity against a range of methicillin and vancomycin-resistant Staphylococcus aureus strains. Structure-activity relationship (SAR) studies revealed that modifications of the core scaffold result in reduced antibacterial activity. Mode of action studies investigations showed that lead compound Pt1 did not impair cell division, RNA, protein, or cell wall synthesis, nor did it affect membrane integrity or potential. Instead, akin to the structurally similar anticancer drug cisplatin (CisPt), Pt1 treatment resulted in reduced DNA staining, visible nucleoid compaction, and activation of DNA damage repair responses. Importantly, we could show that Pt1 is able to interact with and damage DNA directly, resulting in DNA strand breaks and fragmentation. Pt1 activity can be reduced significantly by high amounts of a hydroxyl radical scavenger. Derivative Pt8, which retained DNA-damaging activity but was less potent in terms of antibacterial activity, was not affected by the presence of radical scavengers, suggesting that Pt1 possesses a multimodal mechanism. In line with this observation, no resistance development to Pt1 was observed over the course of 36 passages. Finally, we could demonstrate the in vivo activity of Pt1, which significantly reduced the bacterial load in a murine S. aureus skin infection model. Altogether, these findings shed light on the SAR and antibacterial mode of action of a novel class of platinum metalloantibiotics, validate its in vivo efficacy, and pave the way for further exploration of platinum compounds as novel drug candidates with a highly attractive activity profile.

microbiology↗

bioRxiv2025

The ORF6 accessory protein contributes to SARS-CoV-2 virulence and pathogenicity in the naturally susceptible feline model of infection

Here the infection dynamics, replication, and pathogenicity of a recombinant virus containing a deletion of ORF6 (rWA1{Delta}ORF6) on the backbone of the highly virulent SARS-CoV-2 WA1 virus (rWA1) were investigated and compared to the parental rWA1 virus. While both rWA1 and rWA1{Delta}ORF6 viruses replicated efficiently in cultured cells, the rWA1{Delta}ORF6 virus produced smaller plaques, suggesting reduced cell-to-cell spread. Luciferase reporter assays revealed immune suppressing effects of ORF6 on interferon and nuclear factor kappa B (NF-{kappa}B) signaling pathways. Pathogenesis assessment in cats revealed that animals inoculated with rWA1 were lethargic and presented with fever on days 2 and 4 post-infection (pi), whereas rWA1{Delta}ORF6-inoculated animals developed subclinical infection. Additionally, animals inoculated with rWA1{Delta}ORF6 presented reduced infectious virus shedding in nasal and oral secretions and broncho-alveolar lavage fluid when compared with the rWA1-inoculated cats. Similarly, the rWA1{Delta}ORF6-inoculated cats presented reduced virus replication in the respiratory tract as evidenced by lower viral loads and reduced lung inflammation on day 3 and 5 pi when compared to rWA1-inoculated animals. Host gene transcriptomic analysis revealed marked differences in differentially expressed genes (DEG) in the nasal turbinate of animals infected with rWA1 when compared to rWA1{Delta}ORF6. Importantly, type I interferon signaling was significantly upregulated in rWA1{Delta}ORF6 infected cats when compared to rWA1-inoculated animals, which is correlated to the reduced replication of rWA1{Delta}ORF6 in the upper and lower respiratory tracts of infected animals. Collectively, these results demonstrate that the SARS-CoV-2 ORF6 is an important virulence determinant of the virus contributing to the modulation of host antiviral immune responses. IMPORTANCESARS-CoV-2 encodes several proteins that inhibit host interferon responses. The accessory protein ORF6 antagonizes interferon signaling by blocking the nucleocytoplasmic trafficking of key transcription factors. In this study, we showed that ORF6 plays an important role in SARS-CoV-2 pathogenesis. While both rWA1 and rWA1{Delta}ORF6 viruses replicated efficiently in cell culture, the rWA1{Delta}ORF6 presented impaired cell-to-spread and reduced innate immune inhibition as compared to the parental rWA1. Pathogenicity study in the feline model revealed an attenuated phenotype of the rWA1{Delta}ORF6 indicating that the ORF6 is a major virulence determinant of SARS-CoV-2. These results also demonstrate that ORF6 contributed to the feline host range of SARS-CoV-2.

microbiology↗

bioRxiv2024

Naturally occurring N-terminal mutations in SARS-CoV-2 nsp1 impact innate immune modulation but do not affect virus virulence

The non-structural protein 1 (nsp1) of SARS-CoV-2 plays a key role in host innate immune evasion. We identified two deletion variants ({Delta}82-85 and {Delta}83-86) in the N-terminal region of the nsp1 of a SARS-CoV-2 BA.5.2.1 variant recovered from a human patient. Analysis of the sequence databases revealed a frequency of 0.5% of these mutations amongst available SARS-CoV-2 sequences. Structural analysis of the deletion mutant nsp1{Delta}82-85 and nsp1{Delta}83-86 revealed a distortion in the protein pocket when compared to the wild-type nsp1 which may affect protein function. To evaluate the functional relevance of these mutations, we cloned the mutant BA.5.2.1 nsp1{Delta}82-85 and nsp1{Delta}83-86 and wild-type nsp1 proteins in expression plasmids and performed luciferase reporter-based assays to assess activation of the interferon and nuclear factor kappa B (NF-{kappa}B) signalling pathways. Both nsp1{Delta}82-85 and nsp1{Delta}83-86 mutants showed marked decreased ability to inhibit the interferon beta (IFN-{beta}) and NF-{kappa}B pathway activation. To assess the relevance of these deletions in the context of SARS-CoV-2 infection, we generated recombinant viruses carrying the wild type BA.5.2.1 nsp1 or the BA.5.2.1 nsp1{Delta}82-85 and nsp1{Delta}83-86 deletions in the backbone of WA1 strain. In vitro characterization of the recombinant SARS-CoV-2 viruses revealed that the recombinant viruses containing the nsp1{Delta}82-85 and nsp1{Delta}83-86 deletions presented similar plaque size and morphology to those produced by the wild-type rWA1-BA.5.2.1-nsp1 virus, indicating a similar ability of the mutant viruses to spread from cell to cell. Importantly, pathogenesis studies revealed that these mutations did not affect virus virulence and pathogenesis in a hamster model of SARS-CoV-2 infection.

microbiology↗

bioRxiv2024

Transcriptomic profiling of healthy individual-derived LCLs revealed inter-individual variability towards-hypoxia-responsive pathways

Hypoxia, or low oxygen levels, affects various developmental, physiological, and pathological processes. Its been consistently reported that there is an inter-individual variability at genetic and molecular pathways related to oxygen sensing and response. Understanding the underlying variability towards hypoxia sensing and response in health and disease conditions is challenging. The Prakriti stratification method of Ayurveda offers solutions, which classifies healthy individuals into different groups based on multisystem phenotyping. Our lab has previously used this method and provided evidence for the variability in hypoxia responsiveness physiologically among healthy individuals at population levels. Our current study seeks to understand hypoxia sensing and response pathways at cellular levels. We used eight Lymphoblastoid cell lines (LCLs) developed from healthy individuals of extreme Prakriti types. Hypoxia challenge experiments were performed using 0.2% oxygen for 24 and 48 hrs. of chronic hypoxia and captured global transcriptomics profiles. Differentially expressed genes revealed activation of core hypoxia-induced transcriptomic signatures, such as HIF-1 signaling and their metabolic reprogramming in pooled as well as in all Prakriti groups. However, there were Prakriti-specific differences, such as activation of TGF-{beta} mediated ROS and PI3K/AKT/mTOR driven mTORC1 complex in Kapha, downregulation of cholesterol homeostasis and regulation of Phosphoinositide biosynthesis in membrane potential observed in the Pitta group. In contrast, ER stress-induced activation of cell survival response via Unfolded protein response in the Vata group. The Prakriti stratification method will provide a novel method to understand inter-individual differences in hypoxia response pathways. SignificanceHypoxia can significantly impact various aspects of our health and well-being. All nucleated cells sense and respond to hypoxia, depending upon their cellular and metabolic activities. Its wide utility and spatiotemporal regulation make it a crucial target to study. We have used the Prakriti stratification method of Ayurveda to explore hypoxia sensing and response at cellular levels. Lymphoblastoid Cell Lines (LCLs) developed from the peripheral blood of stratified healthy individuals have been utilized to study the expression level variability at the baseline and hypoxia-induced conditions. The outcomes of our study will be crucial to understanding inter-individual variability in response to hypoxia overlayed baseline variations. Resulting in differential susceptibility towards hypoxic response in health and contributes to understanding variable outcomes in disease conditions. Molecular targets from our study will further be utilized for interventional drug targets in hypoxia-induced disease conditions.

cell biology↗

bioRxiv2024

Impaired ovarian development in a zebrafish fmr1 knockout model

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder and the leading genetic cause of autism spectrum disorders. FXS is caused by loss of function mutations in Fragile X mental retardation protein (FMRP), an RNA binding protein that is known to regulate translation of its target mRNAs, predominantly in the brain and gonads. The molecular mechanisms connecting FMRP function to neurodevelopmental phenotypes are well understood. However, neither the full extent of reproductive phenotypes, nor the underlying molecular mechanisms have been as yet determined. Here, we developed new fmr1 knockout zebrafish lines and show that they mimic key aspects of FXS neuronal phenotypes across both larval and adult stages. Results from the fmr1 knockout females also showed that altered gene expression in the brain, via the neuroendocrine pathway contribute to distinct abnormal phenotypes during ovarian development and oocyte maturation. We identified at least three mechanisms underpinning these defects, including altered neuroendocrine signaling in sexually mature females resulting in accelerated ovarian development, altered expression of germ cell and meiosis promoting genes at various stages during oocyte maturation, and finally a strong mitochondrial impairment in late stage oocytes from knockout females. Our findings have implications beyond FXS in the study of reproductive function and female infertility. Dissection of the translation control pathways during ovarian development using models like the knockout lines reported here may reveal novel approaches and targets for fertility treatments. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/579749v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@15ea8b3org.highwire.dtl.DTLVardef@195838corg.highwire.dtl.DTLVardef@ef8940org.highwire.dtl.DTLVardef@1bd58a_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

molecular biology↗

bioRxiv2023

Repurposing HIV antiretroviral drug efavirenz against chikungunya virus

Chikungunya virus (CHIKV) has frequently recurred in recent decades, causing outbreaks worldwide in tropical and subtropical regions. The re-emergence of CHIKV poses a substantial risk to human health as no efficacious drugs are currently available to curb new outbreaks. Here, the anti-CHIKV activity of efavirenz was investigated by in vitro cell culture-based antiviral assay, immunofluorescence assay (IFA), and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used for treatment of acquired immunodeficiency syndrome (AIDS), and it has good oral bioavailability, long half-life and affordable low cost. This study demonstrated dose-dependent robust anti-CHIKV activity of efavirenz at low micromolar concentration (EC50 = 1.33 {micro}M). To determine potential broad anti-alphavirus activity of efavirenz, its inhibitory activity against Sindbis virus (SINV) was detected. Interestingly, efavirenz also inhibited the replication of SINV at a low micromolar range (EC50 = 0.7 {micro}M). Time of addition assay, direct transfection of virus replicon RNA and minus-sense specific RT-PCR elucidated that efavirenz hinders the viral replication at an early stage after the virus entry by inhibiting the viral RNA synthesis. Efavirenz showed a binding affinity with purified CHIKV capsid protein (CHIKV CP) and it is known that CHIKV CP plays a novel role in the early phase of viral protein synthesis, suggesting CP might be one of the potential protein targets in addition to viral or host proteins involved in viral genome replication. The present study underscores the repurposing of efavirenz for antiviral therapy against CHIKV to curb future viral outbreaks. HighlightsIdentification of in vitro anti-CHIKV activity of efavirenz. Efavirenz disrupts the early phase of virus replication by interfering in the CHIKV minus-sense RNA synthesis. Efavirenz and tomatidine also inhibit SINV replication indicating potential broad spectrum anti-alphavirus activity. Efavirenz holds potential as therapeutic treatment for clinical infections of Chikungunya.

molecular biology↗

bioRxiv2023

Revealing and evaluation of antivirals targeting multiple druggable sites of RdRp complex in SARS-CoV-2

SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) complex consisting of nsp12, nsp7, and nsp8 as the key enzyme for viral genome replication and is a proven antiviral drug target. In this study, molecular interactions of nsp7 and nsp8 with nsp12 and the active site of nsp12 were coterminously targeted using in-silico screening of small molecule libraries to identify potential antivirals. Surface plasmon resonance (SPR) based assay using purified nsp7 and nsp8 proteins was developed, and the binding of identified molecules to targets was validated. The antiviral efficacy of identified small molecules was evaluated using cell-based assays, and potent antiviral effect with EC50 values of 0.56 M, 0.73 M, and 2.8 M was demonstrated by fangchinoline, cepharanthine, and sennoside B, respectively. Further in vivo, investigation using hACE2 mice is being conducted. This is the first study that targets multiple sites in the RdRp complex of SARS-CoV-2 using a structure-based molecular repurposing approach and suggests potential therapeutic options for emerging variants of SARS-CoV-2.

molecular biology↗

bioRxiv2022

Crystal structure and activity profiling of deubiquitinating inhibitors-bound to SARS-CoV-2 papain like protease revealed new allosteric sites for antiviral therapies

SARS-CoV-2 papain-like protease (PLpro) is a key antiviral target as it plays a dual role in viral replication and in modulation of innate immune responses by deubiquitinating or deISGylating host proteins. Thus, therapeutic targeting of PLpro serves as a two-pronged approach to abate SARS-CoV-2. Interestingly, PLpro shares structural and functional similarities with the cellular deubiquitinating enzymes (DUBs) and in this study this fact has been exploited to identify DUBs inhibitors that target the Ubiquitin/ISG15 binding site and the known catalytic substrate binding pocket of PLpro. Among these identified compounds, flupenthixol, lithocholic acid, teneligliptin, and linagliptin markedly inhibited the proteolytic activity of purified PLpro and demonstrated potent antiviral efficacies against SARS-CoV-2 infection in a dose dependent manner. Treatment with lithocholic acid and linagliptin suppressed the expression levels of inflammatory mediators, thereby, restoring immune responses. Crystal structures of SARS-CoV-2 PLpro in complex with linagliptin and with lithocholic acid determined in this study, revealed insights into the inhibition mechanism with unique interactions within the Ubiquitin/ISG15 binding site (S2 site; Phe69, His73, Asn128, His175) and the substrate binding cleft. Additionally, oral and intraperitoneal treatments with linagliptin increased survival, reduced lung viral load, and ameliorated histopathological damage in mouse-adapted model of SARS-CoV-2 infection. The study for the first time demonstrates a two-pronged strategy using DUB inhibitors that target the proteolytic activity of PLpro and simultaneously reinstates the hosts immune response against SARS-CoV-2.

molecular biology↗

bioRxiv2022

Elucidation of the antiviral mechanism of natural therapeutic molecules Herbacetin and Caffeic acid phenethyl ester against Chikungunya and Dengue virus

Chikungunya (CHIKV) and dengue (DENV) viruses pose a public health risk and lack antiviral treatment. Structure-based virtual screening of natural MTase substrates library identified herbacetin (HC) and caffeic acid phenethyl ester (CAPE) as potential CHIKV nsP1 and DENV NS5 MTase inhibitors. Binding affinities and MTase inhibition were confirmed using purified proteins. Crystal structure of DENV3 NS5 MTase and CAPE complex revealed CAPE binding at GTP and cap 0 RNA sites. Interestingly, HC and CAPE depleted polyamines, which are crucial for RNA virus replication, and effectively diminished replication with IC50 values of [~]13.44 {micro}M and [~]0.57 {micro}M against CHIKV, and [~]7.24 {micro}M and [~]1.01 {micro}M against DENV, respectively. Polyamine addition did not reverse the antiviral effects, suggesting a dual inhibition mechanism. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/494145v5_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1f579eforg.highwire.dtl.DTLVardef@11862eborg.highwire.dtl.DTLVardef@67276org.highwire.dtl.DTLVardef@144c7f8_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

Whole exome-sequencing of vitiligo lesions indicate lower burden of somatic variations: implications in risk for non-melanoma skin cancers

Mapping of somatic variations has enabled understanding the progression of clonal variations from healthy skin to cutaneous malignancies. Highlighting, the adaptive nature of pigmentation, germline mutations in albinism amplify skin cancer susceptibility. However, lower incidence of non-melanoma skin cancer among subjects with acquired depigmenting skin disorder vitiligo is enigmatic and a matter of longstanding debate. To address this, we performed high-coverage exome sequencing of matched non-lesional and lesional vitiligo skin along with whole blood to account for germline variations. Our analysis suggests lower burden of somatic cancer-associated variations in exposed depigmented lesional skin compared to the non-lesional skin. A detailed investigation of vitiligo skin transcriptome reveals elevation of DNA repair and cell-proliferation pathways. Validation by comet-assay for DNA damage and cell cycle analysis of epidermal cells suggest undamaged DNA in vitiligo lesions that could be attributed to higher proliferation-coupled repair. Endorsing this, UV-signature variations are not prominent, instead SBS5 associated with endogenous mutational processes is conspicuous in both the vitiligo tissues. Our systematic pilot study indicates lower somatic mutation burden in vitiligo skin and supports the earlier demographic observation on lower risk of non-melanoma skin cancer in vitiligo subjects, providing an opportunity to learn strategies for cancer prevention from vitiligo. Brief SummaryVitiligo skin harbors decreased somatic variation burden in cancer-associated genes and a concomitant augmentation in DNA repair response, explaining the lower incidence of cutaneous malignancies.

genomics↗

bioRxiv2022

An efficient and cost-effective method for directed mutagenesis at multiple dispersed sites - a case study with Omicron Spike DNA

Site directed mutagenesis is an invaluable technique which enables the elucidation of the contribution of specific residues to protein structure and function. The simultaneous introduction of mutations at a large number of sites (>10), singly and in multiple combinations is often necessary to fully understand the functional contributions. We report a simple, efficient, time and cost effective method to achieve this using commonly available molecular biology reagents and protocols, as an alternative to gene synthesis. We demonstrate this method using the Omicron Spike DNA construct as an example, and create a construct bearing 37 mutations (as compared to wild-type Spike DNA), as well as four other constructs bearing subsets of the full spectrum of mutations. We believe that this method can be an excellent alternative to gene synthesis, especially when three or more variants are required. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

molecular biology↗

bioRxiv2021

GA-mediated spatial control of cell division expounds the leaf size variation between cultivated and wild rice

O_LICellular and genetic understanding of rice leaf size regulation is limited, despite rice being the staple food of more than half of the global population. We investigated the mechanism controlling the rice leaf length using cultivated and wild rice accessions that remarkably differed for leaf size. C_LIO_LIComparative transcriptomics, Gibberellic Acid (GA) quantification, and leaf kinematics of the contrasting accessions suggested the involvement of GA, cell cycle, and Growth-Regulating Factors (GRFs) in the rice leaf size regulation. Zone-specific expression analysis and VIGS established the functions of specific GRFs in the process. C_LIO_LIThe leaf length of the selected accessions was strongly correlated with GA levels. Higher GA content in wild rice accessions with longer leaves and GA-induced increase in the leaf length via an increase in cell division confirmed a GA-mediated regulation of division zone in rice. Downstream to GA, OsGRF7 and OsGRF8 function for controlling cell division to determine the rice leaf length. C_LIO_LISpatial control of cell division to determine the division zone size mediated by GA and downstream OsGRF7 and OsGRF8 explains the leaf length differences between the cultivated and wild rice. This mechanism to control rice leaf length might have contributed to optimizing leaf size during domestication. C_LI

plant biology↗