General Assessment
This study makes a convincing case that centromeric noncoding RNAs play
an important role in chromosomal integrity, and also provides an RNA
transcript set that will facilitate future studies of centromere
transcription. Given the difficulty of targeting highly repetitive
centromeric sequence, the presented data and interpretations make
impressive demonstrations on cenRNA localization and function. In
particular, the in vivo immunofluorescence experiments clearly
demonstrate that an individual cenRNA (cenRNA#4) localizes near
centromeres. If the authors choose to make an addition to the study,
they may consider adding an IF image of cells experiencing chromosomal
segregation defects, as it would help illustrate the direct observations
to readers who are unfamiliar with the field. In addition, future
readers with backgrounds in genomics will likely be interested in
knowing the defining feature of each of the four identified cenRNA
classes, and whether cenRNA loci are generally near canonical promoters
and/or polyadenylation signals. Overall, this work contributes exciting
findings in support of a fascinating model that explains how centromeric
RNAs target and load CENP-A protein to the centromere, ensuring proper
chromosomal segregation during mitosis.