Interpretations
One major claim of this paper is that the knockdown of cenRNA#4 leads to chromosomal segregation defects. The explanatory model is that the cenRNA is responsible for binding and loading CENP-A to the centromere, and that segregation defects occur upon depletion of the cenRNA due to a lack of CENP-A. In Figure 4, the authors demonstrate that a higher proportion of cells experience segregation defects in HeLa cells by IF with 𝛼-tubulin and CENP-B co-staining. If it were observed in an IF experiment that CENP-A was depleted or found at lower levels in the knockdown conditions, it would provide more support for this mechanistic hypothesis. A more speculative claim of the paper is that because the authors observe fewer foci of 𝛼-satellite RNAs in HeLa nuclei than centromeres, cenRNAs may bind to centromeres in trans. This hypothesis is sound, yet could incorporate more support from further IF experiments that definitively show that one cenRNA deriving from one chromosome is localized to a different chromosome.