Biology subjects

Soni, I.

Publications and source records attributed to Soni, I..

5 recordsLinked to original sources

bioRxiv2026

Operon-driven antagonism and novel modulation of DNA damage sensor STPK specific PP2C phosphatase in Deinococcus radiodurans

This study identifies a novel operon-driven signaling module in Deinococcus radiodurans. The operon includes a von Willebrand A domain protein (DRA0331), a Ser/Thr protein kinase (DRA0332), a canonical FHA-domain protein (DRA0333), and a PP2C-type phosphatase (DRA0334). DRA0334 shows Mn{superscript 2}{square}-dependent phosphatase activity and has a unique dual-domain structure that combines a Kinase-Interacting FHA (KI-FHA) domain with a PP2C catalytic domain. Functional assays show that FHA-domain protein, DRA0333 boosts the phosphorylation of STPKs like RqkA and DR1243 while operonic partner PP2C-type phosphatase, DRA0334 counteracts this through targeted dephosphorylation, establishing a phospho-regulatory antagonism. Notably, the KI-FHA domain of the DRA0334 phosphatase competitively interacts with the FHA domain to modulate the radiation-responsive RqkA kinase, thereby maintaining kinase-phosphatase balance. This KI-FHA domain also imparts substrate specificity and enables feedback regulation. Additionally, DRA0334 modular variants confirm separate roles of catalytic and docking modules, and STRING analyses link DRA0334 functions to DNA repair and stress recovery. Collectively, the findings suggest an operonic connection between DRA0333 and DRA0334, indicating that the KI-FHA and FHA domains may act as phospho-docking switches. These switches can regulate both kinase and phosphatase activities in a push-pull regulatory mechanism within the phosphorylation-dephosphorylation cycle of signal transduction, depending on their association with the type of catalytic domain.

molecular biology↗

bioRxiv2024

Surviving the Storm: Exploring the Role of Natural Transformation in Nutrition and DNA Repair of Stressed Deinococcus radiodurans

Deinococcus radiodurans, a natural transformation (NT) enabled bacterium renowned for its exceptional radiation resistance, employs unique DNA repair and oxidative stress mitigation mechanisms as a strategic response to DNA damage. This study excavate into the intricate roles of NT machinery in the stressed D. radiodurans, focusing on the genes comEA, comEC, endA, pilT and dprA, which are instrumental in the uptake and processing of extracellular DNA (eDNA). Our data reveals that NT not only supports the nutritional needs of D. radiodurans under stress but also have roles in DNA repair. The study findings establish that NT-specific proteins (ComEA, ComEC, and EndA) might contribute to support the nutritional requirements in unstressed and heavily DNA-damaged cells while DprA contribute differently and in a context-dependent manner to navigating through the DNA damage storm. Thus, this dual functionality of NT-specific genes is proposed to be one of factor in D. radiodurans remarkable ability to survive and thrive in environments characterized by high levels of DNA-damaging agents. Author SummaryDeinococcus radiodurans, a bacterium known for its extraordinary radiation resistance. This study explores the roles of natural transformation (NT) machinery in the radiation-resistant bacterium Deinococcus radiodurans, focusing on the genes comEA, comEC, endA, pilT, and dprA. These genes are crucial for the uptake and processing of extracellular DNA (eDNA) and contribute to the bacterium nutritional needs and DNA repair under stress. The findings suggest that the NT-specific proteins ComEA, ComEC, and EndA may help meet the nutritional needs of unstressed and heavily DNA-damaged cells, whereas DprA plays a distinct role that varies depending on the context in aiding cells to cope with DNA damage. The functionality of NT genes is proposed to enhance D. radiodurans survival in environments with high levels of DNA-damaging agents.

molecular biology↗

bioRxiv2023

The stress-induced lincRNA JUNI is a critical factor for cancer cell survival whose interactome is a prognostic signature in clear cell renal cell carcinoma

Cancer cells rely on adaptive mechanisms to survive the multiple stressors they encounter, including replication stress, toxic metabolic products and exposure to genotoxic drugs. Understanding the factors involved in these stress responses is crucial for developing effective treatments. Here, we describe a previously unstudied long non-coding RNA (lncRNA), JUNI (JUN-DT, LINC01135), which is regulated by MAPK and responsive to stress. JUNI positively regulates the expression of its neighboring gene JUN, a key transducer of signals that regulate multiple transcriptional outputs. Our findings reveal that silencing JUNI sensitizes cancer cells to chemotherapeutic drugs or UV radiation, and that its prolonged silencing leads to cell death regardless of stress exposure, highlighting the pro-survival importance of JUNI. We identified 57 proteins that interact with JUNI and found that the activity of one of them, the MAPK phosphatase and inhibitor DUSP14, is inhibited by JUNI. This effect results in c-Jun induction following exposure of cancer cells to UV radiation and promotes cellular survival. Although JUNI regulates c-Jun and its downstream targets, the pro-survival effects in cells not exposed to stress are only partially dependent on c-Jun regulation. JUNI expression levels significantly correlate with patients survival across 11 different types of cancer. Interestingly, the correlation of DUSP14 expression levels with patients survival in nine of these tumors is coherently inverse, indicating contradicting effects that are relevant not only for c-Jun induction and cellular survival but also in human cancer. Notably, we observed particularly significant antagonistic correlations in clear cell renal cell carcinoma (ccRCC) (p=5.7E-05 for JUNI and p=2.9E- 05 for Dusp14). In fact, the expression levels of 76% of JUNI-interacting proteins predict the prognosis of ccRCC patients significantly. Furthermore, a combined hazard ratio calculation demonstrates that this gene combination serves as a highly specific prognostic signature for ccRCC. Overall, our findings reveal a new important factor in stress signaling and cellular survival that is involved in ccRCC.

cell biology↗

bioRxiv2023

Natural transformation specific DprA coordinate DNA double strand break repair pathways in heavily irradiated D. radiodurans

Deinococcus radiodurans exhibits remarkable survival under extreme conditions, including ionizing radiation, desiccation, and various DNA-damaging agents. It employs unique repair mechanisms, such as single-strand annealing (SSA) and extended synthesis-dependent strand annealing (ESDSA), to efficiently restore damaged DNA fragments. In this study, we investigate the regulatory role of the NT-specific protein DprA in DNA repair pathways following acute gamma radiation exposure. Our findings demonstrate that the absence of DprA leads to rapid repair of gamma radiation-induced DNA double-strand breaks (DSBs), with diminished involvement of the ESDSA pathway. Furthermore, our data suggest that the SSA pathway becomes the primary mechanism for DNA DSB repair in the absence of DprA. Overall, our results highlight the regulatory function of DprA in modulating the choice between SSA and ESDSA pathways for DNA repair in the radiation-resistant bacterium D. radioduransx.

cell biology↗

bioRxiv2022

Cancer cells survival is dependent on the lincRNA JUNI

Identification of key factors for cellular survival is a basis for therapy. We identified JUNI (linc01135) as a stress-regulated lncRNA, essential for cell survival and implicated in cancer. Besides regulating c-Jun expression we demonstrate c-Jun-independent, robust requirement for cell survival. Analysis of median survival of cancer patients suffering from various types of cancer reveals correlations of JUNI expression levels with alterations in patients survival. JUNIs antagonistic interaction with DUSP14, a negative regulator of the JNK pathway, underlies the regulation of c-Jun and partial effects on cellular survival. Consistently, DUSP14 expression is coherently inversely-correlated with the survival of patients suffering from the same types of cancer. Our data suggests that JUNI is a novel master regulator of cell fate. SummaryJUNI is a novel regulator of cell survival, JNK activation and c-Jun expression, implicated in survival of cancer patients

cell biology↗