Deciphering the role of nuclear Arp8 in rRNA Recognition - Role beyond Chromatin Remodelling

Ribosome biogenesis is extremely challenging with respect to energy and resources, its fidelity and rRNA transcription is strictly examined and regulated during cellular stress conditions. The role of CRCs or its components in ribosome biogenesis is not very clear. A wealth of accumulating evidences supports moonlighting functions for DNA repair proteins in the nucleolar function of making ribosomes. Werner syndrome RecQ like helicase (WRN) and Bloom syndrome RecQ like helicase (BLM) are DNA repair proteins having defined role in ribosome biogenesis by regulating the transcription of pre-ribosomal RNA and quality control of rRNA. Arp8 plays important role in DNA repair and cell cycle progression. Arp8 deletion showed decreased resistance to chemical, acidic and oxidative stress than wild type. These interesting observations from PI’s laboratory led them to this proposal to understand the roles of Arp8 beyond chromatin remodelling, especially in ribosomal RNA processing and biogenesis during normal and stress conditions. 

The proposed work will provide a handle to delineate the underlying mechanisms by which genotoxic stress impedes rRNA processing/ribosome biogenesis and how Arp8 is involved in these processes. Given the reputation of Arp8 in DNA repair and importance of ribosome biogenesis in critical cellular processes, the cross talk of these two processes will lead to the identification of novel drug targets and development of novel therapeutics.