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Determinants of minor satellite RNA function in chromosome segregation in mouse embryonic stem cells.
J. Cell Biol. 223:e202309027 (2024)
The centromere is a fundamental higher-order structure in chromosomes ensuring their faithful segregation upon cell division. Centromeric transcripts have been described in several species and suggested to participate in centromere function. However, low sequence conservation of centromeric repeats appears inconsistent with a role in recruiting highly conserved centromeric proteins. Here, we hypothesized that centromeric transcripts may function through a secondary structure rather than sequence conservation. Using mouse embryonic stem cells (ESCs), we show that an imbalance in the levels of forward or reverse minor satellite (MinSat) transcripts leads to severe chromosome segregation defects. We further show that MinSat RNA adopts a stem-loop secondary structure, which is conserved in human α-satellite transcripts. We identify an RNA binding region in CENPC and demonstrate that MinSat transcripts function through the structured region of the RNA. Importantly, mutants that disrupt MinSat secondary structure do not cause segregation defects. We propose that the conserved role of centromeric transcripts relies on their secondary RNA structure.
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Publication type
Article: Journal article
Document type
Scientific Article
ISSN (print) / ISBN
0021-9525
e-ISSN
1540-8140
Journal
Journal of Cell Biology, The
Quellenangaben
Volume: 223,
Issue: 7,
Article Number: e202309027
Publisher
Rockefeller University Press
Non-patent literature
Publications
Reviewing status
Peer reviewed
Grants
Helmholtz Association