Determinants of minor satellite RNA function in chromosome segregation in mouse embryonic stem cells
JCB Report from the Torres-Padilla Lab
16.04.2024
Yung-Li Chen, Alisha N. Jones, Amy Crawford, Michael Sattler, Andreas Ettinger, Maria-Elena Torres-Padilla (2024 April 16) Determinants of minor satellite RNA function in chromosome segregation in mouse embryonic stem cells. Journal of Cell Biology 223(7): e202309027. https://doi.org/10.1083/jcb.202309027
Summary from the article profile:
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.