Authors: Muhammad Shuaib, Krishna Mohan Parsi, Hideya Kawaji, Manjula Thimma, Sabir Abdu Adroub, Alexandre Fort, Yanal Ghosheh, Tomohiro Yamazaki, Taro Mannen, Loqmane Seridi, Bodor Fallatah, Waad Albawardi, Timothy Ravasi, Piero Carninci, Tetsuro Hirose, Valerio Orlando

Institutions: 

  • King Abdullah University of Science and Technology (KAUST), BESE Division, KAUST Environmental Epigenetics Program, Thuwal, 23955-6900, Saudi Arabia
  • IRCSS Fondazione Santa Lucia, Epigenetics and Genome Reprogramming, Rome, Italy.
  • RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan

Publication: Biorxiv

Date: January 2019

Full paper: https://www.biorxiv.org/content/10.1101/525527v1

Abstract:

Aside from their roles in the cytoplasm, RNA-interference components have been reported to localize also in the nucleus of human cells. In particular, AGO1 associates with active chromatin and appears to influence global gene expression. However, the mechanistic aspects remain elusive. Here, we identify AGO1 as a paraspeckle component that in combination with the NEAT1 lncRNA maintains 3D genome architecture. We demonstrate that AGO1 interacts with NEAT1 lncRNA and its depletion affects NEAT1 expression and the formation of paraspeckles. By Hi-C analysis in AGO1 knockdown cells, we observed global changes in chromatin organization, including TADs configuration, and A/B compartment mixing. Consistently, distinct groups of genes located within the differential interacting loci showed altered expression upon AGO1 depletion. NEAT1 knockout cells displayed similar changes in TADs and higher-order A/B compartmentalization. We propose that AGO1 in association with NEAT1 lncRNA can act as a scaffold that bridges chromatin and nuclear bodies to regulate genome organization and gene expression in human cells.