Xist lncRNA forms silencing granules that induce heterochromatin formation and repressive complexes recruitment by phase separation

作者: Andrea Cerase , Alexandros Armaos , Fernando Cid , Philip Avner , Gian Gaetano Tartaglia

DOI: 10.1101/351015

关键词: Cell biologyChemistryRNAXISTInteractomeX-inactivationPhase (matter)Gene silencingRibonucleoproteinStress granule

摘要: Xist long non-coding RNA induces heterochromatinization of the X-chromosome by accumulating in large ribonucleoprotein assemblies. We suggest that regulates X chromosome inactivation recruiting RNA-binding proteins via a mechanism liquid-liquid phase separation. To support this hypothesis, we provide evidence forms condensates are similiar size, shape and protein composition to paraspeackles stress granules. show interactome is particularly enriched intrinsically disordered capable separating. reinforces Xi sequestering repressive complexes, such as Polycomb proteins, an indirect way through This process complementary canonical chromatin-mediated recruitment.

参考文章(62)
Ellen Gelpi, Benedetta Bolognesi, Lies-Anne Wfm Severijnen, Benjamin Lang, Gian Gaetano Tartaglia, Riccardo Delli Ponti, Teresa Botta-Orfila, Nieves Lorenzo-Gotor, Iona Gelabert-Baldrich, Fernando Cid-Samper, Renate K. Hukema-Felten, Phase Separations Driven by RNA Scaffolds and Protein Sequestration in FXTAS bioRxiv. pp. 298943- ,(2018) , 10.1101/298943
Shovamayee Maharana, Jie Wang, Dimitrios K. Papadopoulos, Doris Richter, Andrey Pozniakovsky, Ina Poser, Marc Bickle, Sandra Rizk, Jordina Guillén-Boixet, Titus M. Franzmann, Marcus Jahnel, Lara Marrone, Young-Tae Chang, Jared Sterneckert, Pavel Tomancak, Anthony A. Hyman, Simon Alberti, RNA buffers the phase separation behavior of prion-like RNA binding proteins Science. ,vol. 360, pp. 918- 921 ,(2018) , 10.1126/SCIENCE.AAR7366
Gang Wan, Brandon D. Fields, George Spracklin, Aditi Shukla, Carolyn M. Phillips, Scott Kennedy, Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance. Nature. ,vol. 557, pp. 679- 683 ,(2018) , 10.1038/S41586-018-0132-0
Asun Monfort, Giulio Di Minin, Andreas Postlmayr, Remo Freimann, Fabiana Arieti, Stéphane Thore, Anton Wutz, Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells Cell Reports. ,vol. 12, pp. 554- 561 ,(2015) , 10.1016/J.CELREP.2015.06.067
Benoit Moindrot, Andrea Cerase, Heather Coker, Osamu Masui, Anne Grijzenhout, Greta Pintacuda, Lothar Schermelleh, Tatyana B. Nesterova, Neil Brockdorff, A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing Cell Reports. ,vol. 12, pp. 562- 572 ,(2015) , 10.1016/J.CELREP.2015.06.053
A. Minajigi, J. E. Froberg, C. Wei, H. Sunwoo, B. Kesner, D. Colognori, D. Lessing, B. Payer, M. Boukhali, W. Haas, J. T. Lee, A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation Science. ,vol. 349, ,(2015) , 10.1126/SCIENCE.AAB2276
Greta Pintacuda, Andrea Cerase, X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells Stem Cell Reviews and Reports. ,vol. 11, pp. 699- 705 ,(2015) , 10.1007/S12015-015-9597-5
Hongjae Sunwoo, John Y. Wu, Jeannie T. Lee, The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, pp. 201503690- ,(2015) , 10.1073/PNAS.1503690112
Simão Teixeira da Rocha, Valentina Boeva, Martin Escamilla-Del-Arenal, Katia Ancelin, Camille Granier, Neuza Reis Matias, Serena Sanulli, Jen Chow, Edda Schulz, Christel Picard, Syuzo Kaneko, Kristian Helin, Danny Reinberg, A Francis Stewart, Anton Wutz, Raphaël Margueron, Edith Heard, Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome Molecular Cell. ,vol. 53, pp. 301- 316 ,(2014) , 10.1016/J.MOLCEL.2014.01.002
Aditi Kanhere, Keijo Viiri, Carla C. Araújo, Jane Rasaiyaah, Russell D. Bouwman, Warren A. Whyte, C. Filipe Pereira, Emily Brookes, Kimberly Walker, George W. Bell, Ana Pombo, Amanda G. Fisher, Richard A. Young, Richard G. Jenner, Short RNAs Are Transcribed from Repressed Polycomb Target Genes and Interact with Polycomb Repressive Complex-2 Molecular Cell. ,vol. 38, pp. 675- 688 ,(2010) , 10.1016/J.MOLCEL.2010.03.019