Biology subjects

Shrivastava, N.

Publications and source records attributed to Shrivastava, N..

3 recordsLinked to original sources

bioRxiv2025

Interactions of Natural Compounds and Biomolecules with Hepatitis C Virus RNA Untranslated Regions: Exploring Structural Modifications to Advance Pathogenesis Understanding and Antiviral Strategy Design

Hepatitis C virus (HCV), a 10 kb positive-strand RNA virus, primarily infects liver cells and is a major cause of liver cirrhosis, which can progress to hepatocellular carcinoma. The HCV RNA untranslated regions (UTRs) adopt topologies that serve as binding sites for host proteins and miRNAs, crucial for viral replication and pathogenesis. However, the precise interactors and mechanisms of these interactions remain unclear. This study investigates the architectural landscape of HCV UTRs alone and in the presence of various interactors. Structural analysis reveals stable HCV UTR topologies, but significant alterations occur upon interaction with miRNAs and phytochemicals, potentially critical for viral pathogenicity. Additionally, proteins SRSF7 and AKAP8L are identified as novel interactors, which could have implication in host immune evasion and enhanced virulence. These findings highlight new miRNAs, proteins, and small molecules as interactors of HCV UTRs, offering insights into HCV infectivity and therapeutic targets for antiviral interventions.

molecular biology↗

bioRxiv2025

eIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by novel small molecules

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis; effects which are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia inducible factors (HIFs). However, translational effects in hypoxia, that likely precede transcriptional effects, have remained largely unexplored. Using ribosome-profiling, we uncovered a selective translational response in acute hypoxia that is eIF3d/eIF3e-dependent and controls downstream hypoxic responses including HIF1a accumulation and cellular invasion. We further demonstrated that eIF3e copy number and an eIF3e-expression signature are associated with worsened outcomes for breast cancer patients. Finally, we identified a class of novel small molecules that target eIF3e specifically, reducing the translational response to hypoxia and to ER stress, another stressor that is dependent on eIF3d/eIF3e-mediated translation. Our data uncover critical functions for eIF3d/eIF3e in the hypoxic response and identify a potential means to inhibit stress-induced translation, and potentially plasticity and metastasis, mediated by eIF3e.

cancer biology↗

bioRxiv2021

NR2F1 is a barrier to dissemination of early-evolved mammary cancer cells

SO_SCPLOWUMMARYC_SCPLOWCancer cells disseminate during very early and sometimes asymptomatic stages of tumor progression. Granted that biological barriers to tumorigenesis exist, there must also be limiting steps to early dissemination, all of which remain largely unknown. We report that the orphan nuclear receptor NR2F1/COUP-TF1 serves as a barrier to early dissemination. High-resolution intravital imaging revealed that loss of function of NR2F1 in HER2+ early cancer cells increased in vivo dissemination without accelerating mammary tumor formation. NR2F1 expression was positively regulated by the tumor suppressive MMK3/6-p38-MAPK pathway and downregulated by HER2 and Wnt4 oncogenic signaling. NR2F1 downregulation by HER2 in early cancer cells led to decreased E-cadherin expression and {beta}-catenin membrane localization, disorganized laminin 5 deposition, and increased expression of CK14, TWIST1, ZEB1 and PRRX1. Our findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 downstream of HER2 signaling.

cancer biology↗