PubMed ID

19704020

UMMS Affiliation

Department of Cell Biology

Date

8-26-2009

Document Type

Article

Subjects

Animals; Cell 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

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: J Cell Biol. 2009 Aug 24;186(4):491-507. Link to article on publisher's site

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Link to Article in PubMed