Life Sciences & Biotechnology
Title : | Deciphering The Role Of Nuclear Actin Related Protein 8 (ARP8) In rRNA Recognition - A Role Beyond Chromatin Remodeling |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Saravanan Matheshwaran, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | saran@iitk.ac.in |
Equipments : | Western Blott apparatus
Bead beater
Incubator |
Details
Executive Summary : | Actin-related proteins (Arps) and conventional actin are crucial components of Chromatin Remodelling Complexes (CRCs), with Arp8 being a key component in the INO80 CRC. Deletion of Arp8 reduces the overall ATPase activity of the INO80 complex and mimics an INO80 null mutant. Arp8 plays a significant role in DNA repair and cell cycle progression. It independently localizes with mitotic chromosomes, suggesting divergent functions during mitosis. Proteome-wide analysis in yeast has revealed Arp8 as a possible mRNA binding protein, and its overexpression has been linked to RNA accumulation. Yeast Arp8 (yArp8) localizes within the nucleolus, an area rich in ribosomal RNA. The yArp8 null mutant showed altered ribosome profiles, abnormal vacuolar morphology, and temperature-sensitive phenotype. Ribosome biogenesis is challenging due to energy and resources, and its fidelity and transcription are closely examined during cellular stress conditions. Arp8 deletion decreased resistance to chemical, acidic, and oxidative stress compared to the wild-type. This proposal aims to understand Arp8's roles beyond chromatin remodelling, particularly in ribosomal RNA processing and biogenesis during normal and stress conditions. The study will focus on genotoxic stress, rRNA processing/export, and ribosome biogenesis. The cross-talk of these processes could lead to the identification of novel drug targets and the development of novel therapeutics. |
Total Budget (INR): | 67,21,264 |
Organizations involved