MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization

Nat Genet. 2018 Jul;50(7):990-1001. doi: 10.1038/s41588-018-0139-3.

Indrabahadur Singh ¹ ², Adriana Contreras ¹, Julio Cordero ¹ ³ ⁴, Karla Rubio ¹, Stephanie Dobersch ¹, Stefan Günther ⁵, Sylvia Jeratsch ⁶, Aditi Mehta ¹, Marcus Krüger ⁷, Johannes Graumann ⁶, Werner Seeger ⁸ ⁹, Gergana Dobreva ³ ⁴ ¹⁰, Thomas Braun ⁵ ⁹, Guillermo Barreto ¹¹ ¹² ¹³

Affiliations

1 Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
2 Chronic Inflammation and Cancer (F180), German Cancer Research Center (DKFZ), Heidelberg, Germany.
3 Anatomy and Developmental Biology, CBTM, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
4 European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
5 Department of Cardiac Development, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
6 Biomolecular Mass Spectrometry, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
7 Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), and Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
8 Department of Lung Development and Remodeling Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
9 Excellence Cluster Cardio Pulmonary System (ECCPS), the Universities of Giessen and Marburg Lung Center (UGMLC), and the German Center of Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Giessen, Germany.
10 Origin of Cardiac Cell Lineages, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
11 Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany. guillermo.barreto@mpi-bn.mpg.de.
12 Excellence Cluster Cardio Pulmonary System (ECCPS), the Universities of Giessen and Marburg Lung Center (UGMLC), and the German Center of Lung Research (Deutsches Zentrum für Lungenforschung, DZL), Giessen, Germany. guillermo.barreto@mpi-bn.mpg.de.
13 Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation. guillermo.barreto@mpi-bn.mpg.de.

PMID: 29867223 DOI: 10.1038/s41588-018-0139-3

Abstract

The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the MicroRNA Mirlet7d as a key regulator of bidirectionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and the polycomb repressive complex 2 (PRC2) to the bidirectionally active loci. The exosome degrades the ncRNAs, whereas PRC2 induces heterochromatin and transcriptional silencing through EZH2. Moreover, this multicomponent RNA-protein complex, which we named MiCEE, tethers the regulated genes to the perinucleolar region and thus is required for proper nucleolar organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bidirectionally expressed genes and global genome organization.

Name
Email *

	Sorry, but the email address you supplied was invalid.