title: Long non-coding RNAs as targets for cytosine methylation.
abstract: Post-synthetic modifications of nucleic acids have long been known to affect their functional and structural properties. For instance, numerous different chemical modifications modulate the structural organization, stability or translation efficiency of tRNAs and rRNAs. In contrast, little is known about modifications of poly(A)RNAs. Here, we demonstrate for the first time that the two well-studied regulatory long non-coding RNAs HOTAIR and XIST are targets of site-specific cytosine methylation. In both XIST and HOTAIR, we found methylated cytosines located within or near functionally important regions that are known to mediate interaction with chromatin-associated protein complexes. We show that cytosine methylation in the XIST A structure strongly affects binding to the chromatin-modifying complex PRC2 in vitro. These results suggest that cytosine methylation may serve as a general strategy to regulate the function of long non-coding RNAs.
authors.affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Amort
authors.forename: Marie F
authors.initials: MF
authors.lastname: Soulière
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wille
authors.forename: Xi-Yu
authors.initials: XY
authors.lastname: Jia
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Hildegard
authors.initials: H
authors.lastname: Wörle
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lusser
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D003596:Cytosine / Q000378:metabolism*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; C561566:HOTAIR long untranslated RNA, human; D063146:Polycomb-Group Proteins; D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA; D003596:Cytosine
keywords: 5-methylcytosine; HOTAIR RNA; RNA methylation; XIST RNA; chromatin; long non-coding RNA; polycomb repressive complex 2