Long non-coding RNAs as targets for cytosine methylation

被引:119
作者
Amort, Thomas [1 ]
Souliere, Marie F. [2 ,3 ]
Wille, Alexandra [1 ]
Jia, Xi-Yu [4 ]
Fiegl, Heidi [5 ]
Woerle, Hildegard [1 ]
Micura, Ronald [2 ,3 ]
Lusser, Alexandra [1 ]
机构
[1] Med Univ Innsbruck, Bioctr, Div Mol Biol, A-6020 Innsbruck, Austria
[2] Univ Innsbruck, Dept Organ Chem, A-6020 Innsbruck, Austria
[3] Univ Innsbruck, Ctr Mol Biosci CMBI, A-6020 Innsbruck, Austria
[4] Zymo Res Corp, Irvine, CA USA
[5] Med Univ Innsbruck, Dept Obstet & Gynecol, A-6020 Innsbruck, Austria
基金
奥地利科学基金会;
关键词
long non-coding RNA; 5-methylcytosine; RNA methylation; chromatin; polycomb repressive complex 2; XIST RNA; HOTAIR RNA; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; CHEMICAL SYNTHESIS; DNA METHYLATION; X-CHROMOSOME; BASE-PAIRS; 5-METHYLCYTOSINE; 5-HYDROXYMETHYLCYTOSINE; EPIGENETICS; BINDING;
D O I
10.4161/rna.24454
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1003 / 1009
页数:7
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