Abstract
Heat shock activates the transcription of arrays of Satellite III (SatIII) DNA repeats in the pericentromeric heterochromatic domains of specific human chromosomes, the longest of which is on chromosome 9. Long non-coding SatIII RNAs remain associated with transcription sites where they form nuclear stress bodies or nSBs. The biology of SatIII RNAs is still poorly understood. Here, we show that SatIII RNAs and nSBs are detectable up to four days after thermal stress and are linked to defects in chromosome behavior during mitosis. Heat shock perturbs the execution of mitosis. Cells reaching mitosis during the first 3 h of recovery accumulate in pro-metaphase. During the ensuing 48 h, this block is no longer detectable; however, a significant fraction of mitoses shows chromosome segregation defects. Notably, most of lagging chromosomes and chromosomal bridges are bound to nSBs and contain arrays of SatIII DNA. Disappearance of mitotic defects at the end of day 2 coincides with the processing of long non-coding SatIII RNAs into a ladder of small RNAs associated with chromatin and ranging in size from 25 to 75 nt. The production of these molecules does not rely on DICER and Argonaute 2 components of the RNA interference apparatus. Thus, massive transcription of SatIII DNA may contribute to chromosomal instability.
Highlights
Centromeres are structural chromatin domains responsible for the faithful segregation of chromosomes during cell division
Heat shock induces the activation of arrays of repetitive Satellite III (SatIII) DNA and the massive production of long non-coding SatIII RNAs that remain associated with sites of transcription giving rise to nuclear stress bodies [23,29]
SatIII RNA sequences are detectable using quantitative RT-PCR, even in unstressed cells, their abundance drastically increases after heat shock and peaks between 2–6 h of recovery when a 104–105-fold induction is consistently observed [25]
Summary
Centromeres are structural chromatin domains responsible for the faithful segregation of chromosomes during cell division They consist of two distinct regions: the centromere core flanked on both sides by pericentromeric domains. The strongest evidence of the involvement of the RNAi machinery in the processing of pericentromeric RNAs and heterochromatin assembly in vertebrates has been provided by Fukagawa et al [11]. They found that loss of DICER in a chicken-human hybrid cell line carrying human chromosome 21 produces the accumulation of long pericentric Satellite
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