AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

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

AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells

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.

Citation

Shuaib, M., Parsi, K. M., Kawaji, H., Thimma, M., Adroub, S. A., Fort, A., … Orlando, V. (2019). AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells. doi:10.1101/525527

Acknowledgements

We are grateful to Hakan Ozadamand Johan Gibcus from Job Dekker group (University of Massachusetts Medical School, USA) for initial help in Hi-C analysis; Riccardo Aiese Cigliano (Sequentia Biotech) for help in bioinformatic analysis; Ana Maria Suzuki (RIKEN) for help in CAGE-seq; Heno Hwang (scientific illustrator) at KAUST for his help in drawing the image (Figure-8); Christian Froekjaer Jensen for critical reading of the manuscript; KAUST Bioscience Core Lab for providing sequencing facility. The work was supported by EPIGEN-CNR (Italian Ministry of University and Research) and King Abdullah University of Science and Technology (KAUST) to V.O. The grants from the MEXT of Japan to TH (26113002 and 17H03630). The grant for Joint Research Program of IGM, Hokkaido University.

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[Bioproject]
Title: Studying the role of nuclear AGO1 in Chromatin OrganisationPublication Date: 2017-08-17. bioproject: PRJNA398595 Handle: 10754/666483

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