AURKB-mediated effects on chromatin regulate binding versus release of XIST RNA to the inactive chromosome
UMass Chan Affiliations
Department of Cell BiologyDocument Type
Journal ArticlePublication Date
2009-08-26Keywords
AnimalsCell Cycle
Cell Line
Chromatin
Chromosomal Proteins, Non-Histone
Chromosomes
Enzyme Activation
Enzyme Inhibitors
Female
Humans
Indoles
Male
Mediator Complex
Models, Molecular
Protein Phosphatase 1
Protein-Serine-Threonine Kinases
inhibitors
RNA
RNA Interference
RNA, Untranslated
Sulfonamides
Transcription Factors
Transgenes
Cell Biology
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Cell Biol. 2009 Aug 24;186(4):491-507. Link to article on publisher's siteDOI
10.1083/jcb.200811143Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39351PubMed ID
19704020Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1083/jcb.200811143