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Long non-coding RNAs as targets for cytosine methylation
Thomas Amort1, Marie F Soulière, Alexandra Wille
1Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.
RNA Biology
|April 19, 2013
Summary
Cytosine methylation, a modification previously unstudied in poly(A)RNAs, targets regulatory long non-coding RNAs (lncRNAs) like HOTAIR and XIST. This modification impacts their interaction with protein complexes, suggesting a new regulatory mechanism for lncRNA function.
Area of Science:
- Molecular Biology
- Epigenetics
- RNA Biology
Background:
- Post-synthetic modifications of nucleic acids are known to influence RNA structure and function.
- While modifications in transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) are well-documented, modifications in polyadenylated RNAs (poly(A)RNAs) remain largely unexplored.
Purpose of the Study:
- To investigate whether regulatory long non-coding RNAs (lncRNAs) are subject to cytosine methylation.
- To identify specific lncRNAs targeted by cytosine methylation and determine the functional implications of these modifications.
Main Methods:
- Site-specific analysis of cytosine methylation in HOTAIR and XIST lncRNAs.
- In vitro binding assays to assess the effect of cytosine methylation on protein-RNA interactions.
Main Results:
- The study identified site-specific cytosine methylation in both HOTAIR and XIST lncRNAs.
- Methylated cytosines were found in regions critical for interacting with chromatin-associated proteins.
- Cytosine methylation within the XIST A structure significantly impacted its binding to the Polycomb Repressive Complex 2 (PRC2) in vitro.
Conclusions:
- Cytosine methylation is a novel modification found in regulatory lncRNAs HOTAIR and XIST.
- This epigenetic modification can regulate lncRNA function by altering interactions with protein complexes.
- Cytosine methylation represents a potential general mechanism for controlling lncRNA activity.
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