Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts embryo nucleolar precursor bodies

Hamdane, Nourdine and Tremblay, Michel G. and Dillinger, Stefan and Stefanovsky, Victor Y. and Nemeth, Attila and Moss, Tom (2017) Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts embryo nucleolar precursor bodies. GENE, 612. pp. 5-11. ISSN 0378-1119, 1879-0038

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Abstract

The nucleolus is the site of ribosome biogenesis and forms around the actively transcribed ribosomal RNA (rRNA) genes. However, the nucleolus is also implicated in cell cycle regulation, tumour suppression and chromosome segregation and nucleolar disfunction is linked to a wide range of human diseases. Interestingly, the nucleolus is also required for genome reprogramming and the establishment of heterochromatin in the mammalian embryo. Mammalian oocytes contain a subnuclear structure that is believed to be the precursor of the functional nucleolus, the Nucleolar Precursor Body (NPB). But the NPB is also required for the organisation of the zygotic heterochromatin and the establishment of pluripotency. We found that disruption of the mouse Upstream Binding Factor (UBF (UBTF)) gene caused disassembly of somatic nucleoli and the accumulation of the key rRNA gene transcription factors into dense, subnuclear foci resembling NPBs. Here we show that UBF deletion causes the rRNA genes to collapse onto their centromere-proximal chromosomal sites spatially distinct from NPB-like structures, and that these structures contain rRNA gene transcription factors but not all nucleolar proteins. We further find that embryonic NPBs and their surrounding heterochromatin are both disrupted in UBF-null mouse embryos. These embryos also display subnuclear foci containing the rRNA gene transcription factors and arrest development before completing the forth cleavage division. The data suggest that the rRNA gene transcription factors have an intrinsic ability to interact and form a discrete nuclear compartment even in the absence of any rRNA gene activity and that the formation or maintenance of the zygotic NPB and surrounding heterochromatin requires UBF. (C) 2016 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: PREIMPLANTATION MOUSE EMBRYOS; POLYMERASE-I TRANSCRIPTION; FACTOR TTF-I; RIBOSOME BIOGENESIS; MATERNAL NUCLEOLUS; RNA; LOCALIZATION; ORGANIZATION; MAMMALS; OOCYTES; Upstream Binding Factor (UBF/UBTF); Gene inactivation; Ribosome Biogenesis; Ribosomal RNA (rRNA) genes; Nucleolus; Nucleolar Precursor Body (NPB); Mouse cleavage embryos
Subjects: 500 Science > 540 Chemistry & allied sciences
500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie > Lehrstuhl für Biochemie III
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Dec 2018 13:10
Last Modified: 15 Feb 2019 12:25
URI: https://pred.uni-regensburg.de/id/eprint/883

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