The role of non-coding RNAs in Chromosome Segregation through Mechanisms Beyond the Sequence

Chromosome segregation, a fundamental process in cell division, ensures the precise distribution of genetic material to daughter cells. Failure to properly segregate sister chromatids leads to errors in maintenance of genomic stability and aberrations in chromosome number or structure, which can lead to disorders like Down syndrome in humans.

To ensure robustness of this process, numerous factors and protein complexes play a role. Centromeres, located within the chromosomes, serve as attachment points for kinetochores, large protein complexes that guide chromosome segregation by interacting with mitotic spindle microtubules on one and centromeric chromatin on the other side.

Previous research has spotlighted the involvement of non-coding RNAs in regulating chromosome segregation. In mice, these RNAs are transcribed from the minor satellite repeats (MinSats) that correspond to the centromeric regions.

A study by the Torres-Padilla group delves into the mechanisms by which such non-coding RNAs influence chromosome segregation, using mouse embryonic stem cells (mESCs) as a model.

First, they discovered that transcription from either forward or reverse MinSat strands respectively, is vital for kinetochore localization and accurate chromosome segregation. By investigating the nature of binding between the kinetochore complex factor CENPC and the RNA, in collaborative work with Michael Sattler’s group, an expert in RNA structure and function, they have found out that MinSat RNAs adopt a specific RNA stem-loop secondary structure.

Even more, the human satellite transcribed from centromere 21, which shares only 53% of sequence similarity to the mouse MinSat, also adopts a similar secondary structure. Thus, the authors propose a new model where it is not the sequence conservation but rather the structural conservation that is responsible for the role of centromeric non-coding RNAs in chromosome segregation.

This study serves as a reminder to explore less obvious avenues in scientific inquiry. In evolutionary studies, researchers often rely on sequence and transcription patterns, focusing on the most conserved elements. However, this discovery highlights the importance of considering non-conserved elements in evolutionary research, as they can converge to perform similar functions despite sequence differences.

By exploring the structural aspects of these RNAs, researchers deepen our understanding of cellular processes and evolution. Additionally, such investigations offer insights into dysregulations in disease and ageing, potentially leading to new therapies and diagnostics.

Read the full publication here.