AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome.
How XIST RNA strictly localizes across the inactive X chromosome is unknown; however, prophase release of human XIST RNA provides a clue. Tests of inhibitors that mimic mitotic chromatin modifications implicated an indirect role of PP1 (protein phosphatase 1), potentially via its interphase repression of Aurora B kinase (AURKB), which phosphorylates H3 and chromosomal proteins at prophase. RNA interference to AURKB causes mitotic retention of XIST RNA, unlike other mitotic or broad kinase inhibitors. Thus, AURKB plays an unexpected role in regulating RNA binding to heterochromatin, independent of mechanics of mitosis. H3 phosphorylation (H3ph) was shown to precede XIST RNA release, whereas results exclude H1ph involvement. Of numerous Xi chromatin (chromosomal protein) hallmarks, ubiquitination closely follows XIST RNA retention or release. Surprisingly, H3S10ph staining (but not H3S28ph) is excluded from Xi and is potentially linked to ubiquitination. Results suggest a model of multiple distinct anchor points for XIST RNA. This study advances understanding of RNA chromosome binding and the roles of AURKB and demonstrates a novel approach to manipulate and study XIST RNA.
Hall
Lisa L
LL
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Lisa.Hall@umassmed.edu
Byron
Meg
M
Pageau
Gayle
G
Lawrence
Jeanne B
JB
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008297:Male; D056892:Mediator Complex; D008958:Models, Molecular; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
C518294:CBX3 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004791:Enzyme Inhibitors; D007211:Indoles; C416944:MED15 protein, human; D056892:Mediator Complex; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D013449:Sulfonamides; D014157:Transcription Factors; C077885:XIST non-coding RNA; D012313:RNA; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1; C474723:hesperadin
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