Biology subjects

Nath, U.

Publications and source records attributed to Nath, U..

6 recordsLinked to original sources

bioRxiv2025

SIRT2 attenuates stress-induced skeletal muscle atrophy by inhibiting glucocorticoid receptor signaling

Skeletal muscle atrophy occurs in several diseases and is associated with chronic stress. Studies indicate that glucocorticoid receptor signalling is the major signalling pathway that mediates stress-induced muscle degeneration. Although the glucocorticoid signalling pathway is relatively well characterized, there is a need to identify modulators of this pathway that may be useful for drug targeting to ameliorate muscle atrophy. SIRT2 is a mammalian Sirtuin isoform known to mediate the longevity benefits of calorie restriction and exercise. Currently, the role of SIRT2 in regulating stress-induced skeletal muscle atrophy is unclear. Our study found that SIRT2 is a critical regulator of muscle homeostasis and is required to protect against stress-induced muscle atrophy. Interestingly, SIRT2 levels are reduced during glucocorticoid-induced muscle atrophy in mice. SIRT2 depletion exacerbates glucocorticoid-induced reduction in myotube diameter and atrophy gene expression. In contrast, SIRT2 overexpression ameliorates myotube atrophy in primary myotubes. Our findings indicate that SIRT2 knockout mice are susceptible to glucocorticoid-induced muscle atrophy, while muscle-specific SIRT2-transgenic mice exhibit improved muscle function and are protected from glucocorticoid-induced atrophy. Mechanistically, SIRT2 binds to the glucocorticoid receptor to negatively regulate its activity, possibly via deacetylation of critical residues in its DNA-binding domain. Our findings suggest that SIRT2 activation may protect against glucocorticoid-induced skeletal muscle atrophy and serve as a potential therapeutic target for treating muscle atrophy.

pathology↗

bioRxiv2025

The JAW-TCP-FUL genetic axis triggers an early reorientation of cell anisotropy to initiate and drive fertilization-dependent fruit elongation in Arabidopsis

In angiosperms, the ovary grows and develops into a fruit after fertilization, and the seeds are formed within to ensure reproductive success. Although genetic regulators suppressing fertilization-independent fruit growth or parthenocarpy have been identified in the Brassicaceae model Arabidopsis thaliana, the fertilization-dependent activator of fruit growth has not been elucidated. Here, we show that the miR319-regulated TCP transcription factors (JAW-TCPs) directly activate the transcription of the FRUITFULL (FUL) gene and promote fruit morphogenesis. By activating FUL, JAW-TCPs indirectly repress the four valve-margin specifying genes SHATTERPROOF1, SHATTERPROOF2, INDEHISCENT and ALCATRAZ in the valves. Mutating these genes suppresses defects caused by the combined loss of JAW-TCPs and FUL. Through extensive confocal imaging studies, we deciphered the cellular basis of JAW-TCP function revealing that JAW-TCPs promote fruit elongation by triggering the reorientation of cell anisotropy along the length axis at an early growth stage after fertilization. Our study uncovers a fertilization-dependent genetic module driving fruit elongation and sets the stage to identify other genetic regulators in this pathway.

plant biology↗

bioRxiv2025

Identification and Characterization of Interacting Proteins of TARANI/ Ubiquitin Specific Protease-14 in Arabidopsis thaliana

Ubiquitin proteases play a crucial role in protein degradation and turnover by regulating the cleavage of polyubiquitin chains. TARANI/UBIQUITIN SPECIFIC PROTEASE-14 (TNI/UBP14) specifically cleaves Lys-48-linked and linear polyubiquitin chains into mono-ubiquitins. The tni mutant exhibits pleiotropic phenotypes, including cup-shaped leaves, tri-cotyledons, reduced lateral roots, and increased petal number, though the underlying mechanisms driving these phenotypes remain unclear. In this study, we generated TNI transgenic lines and employed immunoprecipitation mass spectrometry, proximity labelling, and yeast two-hybrid screening to identify TNIs interacting proteins. These analyses revealed 92 interactors involved in diverse biological processes, including protein and carbohydrate metabolism, light signalling, and intracellular transport. Subcellular localization analysis showed that many of the interacting proteins are located in the nucleus and cytoplasm, suggesting that TNIs nuclear localization may regulate gene function. We further validated the in planta biological significance of ULTRAPETALA 2 and HASPIN KINASE as key interacting partners of TNI. These findings uncover previously uncharacterized functions of TNI/UBP14, shedding light on its central role in cellular processes and providing insights into its regulatory mechanisms--an area that has remained largely unexplored until now. Summary statementThe proteins that interact with the TARANI/ Ubiquitin protease 14 in vivo have been identified using immunoprecipitation mass-spectrometry methods. Identification of non-overlapping targets highlight the importance of using diverse protein identification methods.

plant biology↗

bioRxiv2024

CUP-SHAPED COTYLEDON2 activates MIR319C transcription and promotes cell proliferation in Arabidopsis leaf primordia

The microRNA miR319 regulates leaf size in diverse plant species by reducing the level of the target transcripts that encode JAW-TCPs, the transcription factors (TF) that restrict leaf size by committing the proliferating pavement cells to differentiation. MIR319C, one of the three miR319-producing genes in Arabidopsis, is expressed throughout the incipient leaf primordia, and its expression domain gets restricted to the base at later stages, partly due to its transcriptional repression by JAW-TCPs. However, the factors that activate and maintain MIR319C expression in leaf primordia are yet unknown. Here, we identify the CUP-SHAPED COTYLEDON2 (CUC2) TF as a direct activator of MIR319C transcription. Using a yeast one-hybrid (Y1H) screen, we identified several NAC domain TFs as potential regulators of MIR319C. Subsequent ex vivo binding and transactivation assays suggested that CUC2 binds to a distal promoter region of the MIR319C locus and activates its transcription. Mutants with compromised CUC2 and MIR319C activities resulted in smaller leaves with fewer cells. Detailed morphometric analysis of higher order CUC2 and MIR319 loss-of-function mutants highlighted the crucial role of the CUC2-MIR319 module in maintaining the duration of cell proliferation in leaf primordia. Additionally, the phenotype of mutants with altered CUC2 and MIR319/JAW-TCP activities demonstrated that CUC2 enhances leaf size through the MIR319C-JAW-TCP pathway. Overall, our findings uncovered a novel role for CUC2 in sustaining cell division by activating MIR319C transcription in the leaf primordia.

plant biology↗

bioRxiv2023

MIR319C and its target JAW-TCPs repress each other and establish cell proliferation pattern in incipient leaf primordia in Arabidopsis thaliana

The microRNA miR319 and its target JAW-TCP transcription factors regulate leaf morphogenesis in diverse plant species. In young Arabidopsis leaf primordia, JAW-TCPs are detected towards the distal region whereas MIR319C is expressed at the base. Little is known about how this complementary expression pattern of MIR319C and JAW-TCPs is generated. Here, we show that MIR319C is initially expressed uniformly throughout the incipient primordia and is later abruptly down-regulated at the distal region, with concomitant distal appearance of JAW-TCPs, when leaves grow to [~]100 {micro}m long. Loss of JAW-TCPs causes distal extension of MIR319C expression domain, whereas ectopic TCP activity restricts MIR319C more proximally. JAW-TCPs are recruited to and are capable of depositing histone H3K27me3 repressive marks on the MIR319C chromatin. JAW-TCPs fail to repress MIR319C in transgenic seedlings where the TCP-binding cis-elements on MIR319C are mutated, causing miR319 gain-of-function-like phenotype. Based on these results, we propose a model for growth patterning in leaf primordia wherein MIR319C and JAW-TCPs repress each other and divide the uniformly growing primordia into distal differentiation zone and proximal proliferation domain. Summary statementJAW-TCPs transcriptionally repress the microRNA319 encoding gene MIR319C to generate their mutually exclusive expression pattern and establish growth polarity during early stages of Arabidopsis leaf primordia.

plant biology↗

bioRxiv2019

The TARANI/ UBIQUITIN SPECIFIC PROTEASE 14 destabilizes the AUX/IAA transcriptional repressors and regulates auxin response in Arabidopsis thaliana

Auxin response is regulated by a group of AUX/IAA transcriptional inhibitors that suppress auxin signaling in the absence of the hormone. While the degradation of these proteins upon auxin signaling has been well studied, the molecular control of their rapid turn-over is not clearly understood. Here, we report that the TARANI/ UBIQUITIN PROTEASE 14 protein in Arabidopsis thaliana (Arabidopsis) is required for AUX/IAA degradation. The tni mutation was originally identified in a forward genetic screen to isolate mutants with altered leaf shape. Detailed phenotypic analysis revealed that tni displays pleiotropic phenotypic alterations that resemble auxin-related defects. The activity of auxin responsive reporters DR5::GUS, DR5::nYFP and IAA2::GUS was reduced in tni organs, implying that TNI is required for normal auxin response. Genetic interaction studies suggested that TNI acts along with TIR1, ARF7, AUX1 and PIN1 - molecules involved in auxin signaling or transport. A map-based cloning approach combined with next-generation sequencing identified TNI as UBIQUITIN SPECIFIC PROTEASE14 which is involved in ubiquitin recycling. In tni, the mutant primary transcript is spliced inefficiently, which is predicted to produce an aberrant protein product in addition to the normal protein, where a polypeptide corresponding to the 3rd intron in inserted in-frame within the Zn-finger domain of UBP14. The tni plants accumulated poly-ubiquitin chains and excess poly-ubiquitinated proteins due to reduced TNI activity. Improper ubiquitin recycling affected the degradation of DII:VENUS, IAA18:GUS and HS::AXR3-NT:GUS, resulting in their stabilization in the tni mutant. Thus, our study identified a function for TNI/UBP14 in regulating auxin response through ubiquitin recycling.

plant biology↗