CENP-A associated lncRNAs influence chromosome segregation in human cells

Transcription occurs ubiquitously throughout non-coding parts of the genome, including at repetitive alpha-satellite DNA elements which comprise the majority of human centromeres. The function of temporally regulated centromeric transcription, and transcripts, is consequently a topic of intense investigation. In this study, we use high throughput approaches to identify and describe lncRNAs associated with the centromere specific histone variant CENP-A that arise from the transcription of specific centromeres at early G1, which we then show are physically associated with centromeres, and which are functionally necessary for accurate chromosome segregation. Targeted depletion of one such centromeric RNA, which originates from a single centromere, is sufficient to increase the frequency of chromosome segregation defects. These data support the emerging paradigm of the necessity of centromere-specific lncRNAs in the integrity of faithful chromosome segregation. RNA-immunoprecipitation followed by Illumina sequencing (RIP-Seq) on chromatin associated or nucleoplasmic RNA.