Universität zu Köln

Singh, Indrabahadur ORCID: 0000-0002-1474-7928, Contreras, Adriana, Cordero, Julio, Rubio, Karla ORCID: 0000-0002-8337-3106, Dobersch, Stephanie, Guenther, Stefan, Jeratsch, Sylvia, Mehta, Aditi, Krueger, Marcus ORCID: 0000-0003-2008-4582, Graumann, Johannes ORCID: 0000-0002-3015-5850, Seeger, Werner ORCID: 0000-0003-1946-0894, Dobreva, Gergana ORCID: 0000-0002-4814-9416, Braun, Thomas ORCID: 0000-0002-6165-4804 and Barreto, Guillermo ORCID: 0000-0002-7777-4712 (2018). MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization. Nature Genet., 50 (7). S. 990 - 1005. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1546-1718

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Singh, Indrabahadur UNSPECIFIED orcid.org/0000-0002-1474-7928 UNSPECIFIED Contreras, Adriana UNSPECIFIED UNSPECIFIED UNSPECIFIED Cordero, Julio UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubio, Karla UNSPECIFIED orcid.org/0000-0002-8337-3106 UNSPECIFIED Dobersch, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Jeratsch, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehta, Aditi UNSPECIFIED UNSPECIFIED UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Graumann, Johannes UNSPECIFIED orcid.org/0000-0002-3015-5850 UNSPECIFIED Seeger, Werner UNSPECIFIED orcid.org/0000-0003-1946-0894 UNSPECIFIED Dobreva, Gergana UNSPECIFIED orcid.org/0000-0002-4814-9416 UNSPECIFIED Braun, Thomas UNSPECIFIED orcid.org/0000-0002-6165-4804 UNSPECIFIED Barreto, Guillermo UNSPECIFIED orcid.org/0000-0002-7777-4712 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-180594
DOI:	10.1038/s41588-018-0139-3
Journal or Publication Title:	Nature Genet.
Volume:	50
Number:	7
Page Range:	S. 990 - 1005
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1546-1718
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RIBOSOMAL-RNA GENES; NONCODING RNA; READ ALIGNMENT; STEM-CELLS; TRANSCRIPTION; EXOSOME; MICRORNAS; HETEROCHROMATIN; DNA; ELEMENTS Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18059