Alpha-satellite RNA transcripts are repressed by centromere–nucleolus associations

Author:

Bury Leah1,Moodie Brittania1,Ly Jimmy12,McKay Liliana S1ORCID,Miga Karen HH3,Cheeseman Iain M12ORCID

Affiliation:

1. Whitehead Institute for Biomedical Research, Cambridge, United States

2. Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

3. UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, United States

Abstract

Although originally thought to be silent chromosomal regions, centromeres are instead actively transcribed. However, the behavior and contributions of centromere-derived RNAs have remained unclear. Here, we used single-molecule fluorescence in-situ hybridization (smFISH) to detect alpha-satellite RNA transcripts in intact human cells. We find that alpha-satellite RNA-smFISH foci levels vary across cell lines and over the cell cycle, but do not remain associated with centromeres, displaying localization consistent with other long non-coding RNAs. Alpha-satellite expression occurs through RNA polymerase II-dependent transcription, but does not require established centromere or cell division components. Instead, our work implicates centromere–nucleolar interactions as repressing alpha-satellite expression. The fraction of nucleolar-localized centromeres inversely correlates with alpha-satellite transcripts levels across cell lines and transcript levels increase substantially when the nucleolus is disrupted. The control of alpha-satellite transcripts by centromere-nucleolar contacts provides a mechanism to modulate centromere transcription and chromatin dynamics across diverse cell states and conditions.

Funder

National Institute of General Medical Sciences

American Cancer Society

G. Harold and Leila Y. Mathers Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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