Loss of centromeric RNA activates the spindle assembly checkpoint in mammalian female meiosis I

Author:

Wu Tianyu1ORCID,Lane Simon I.R.2ORCID,Morgan Stephanie L.3,Tang Feng4,Jones Keith T.5ORCID

Affiliation:

1. Department of Central Laboratory, Clinical Laboratory, Jing'an District Centre Hospital of Shanghai, Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism and Institutes of Biomedical Sciences, the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China

2. Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, UK

3. School of Biological Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK

4. Discipline of Obstetrics and Gynecology, School of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, Australia

5. Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, UK

Abstract

The repetitive sequences of DNA centromeric regions form the structural basis for kinetochore assembly. Recently they were found to be transcriptionally active in mitosis, with their RNAs providing noncoding functions. Here we explore the role, in mouse oocytes, of transcripts generated from within the minor satellite repeats. Depletion of minor satellite transcripts delayed progression through meiosis I by activation of the spindle assembly checkpoint. Arrested oocytes had poorly congressed chromosomes, and centromeres were frequently split by microtubules. Thus, we have demonstrated that the centromeric RNA plays a specific role in female meiosis I compared with mitosis and is required for maintaining the structural integrity of centromeres. This may contribute to the high aneuploidy rates observed in female meiosis.

Funder

Leverhulme Trust

China Postdoctoral Science Foundation

Publisher

Rockefeller University Press

Subject

Cell Biology

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