AGO1 interacts with NEAT1 lncRNA and impacts nuclear compartments

Abstract

Argonaute 1 (AGO1), a central component of the RNA interference (RNAi) pathway, has recently been implicated in nuclear functions, particularly in chromatin organization and gene regulation. However, the role of AGO1 in lncRNA-driven nuclear compartmentalization remains elusive. In this study, we uncover a novel function for AGO1 in the regulation of nuclear architecture through its interaction with the long non-coding RNA (lncRNA) NEAT1. NEAT1 lncRNA is required for the formation of paraspeckles, nuclear substructures involved in multiple cellular processes. We show that AGO1 physically interacts with NEAT1 and other key paraspeckle proteins (PSPs) and co-localizes with paraspeckles in the nucleus. AGO1 depletion disrupts expression of both NEAT1 isoforms, reduces the interaction of essential PSPs with NEAT1 lncRNA, and leads to impaired paraspeckle formation. Furthermore, depletion of NEAT1 results in the mis-localization of AGO1 from paraspeckles and alters active chromatin compartments. Together, our findings establish a new functional relationship between AGO1 and NEAT1 in nuclear compartmentalization and chromatin architecture.