Human Centromeres Produce Chromosome-Specific and Array-Specific Alpha Satellite Transcripts that Are Complexed with CENP-A and CENP-C

Abstract

Human centromeres are defined by alpha satellite DNA arrays that are distinct and chromosome specific. Most human chromosomes contain multiple alpha satellite arrays that are competent for centromere assembly. Here, we show that human centromeres are defined by chromosome-specific RNAs linked to underlying organization of distinct alpha satellite arrays. Active and inactive arrays on the same chromosome produce discrete sets of transcripts in cis. Non-coding RNAs produced from active arrays are complexed with CENP-A and CENP-C, while inactive-array transcripts associate with CENP-B and are generally less stable. Loss of CENP-A does not affect transcript abundance or stability. However, depletion of array-specific RNAs reduces CENP-A and CENP-C at the targeted centromere via faulty CENP-A loading, arresting cells before mitosis. This work shows that each human alpha satellite array produces a unique set of non-coding transcripts, and RNAs present at active centromeres are necessary for kinetochore assembly and cell-cycle progression.