Building on work from the 1970s, the era of orange shag carpet and bell bottoms, researchers report that poly(A) RNA gets methylated on cytosines, just like other RNAs and DNA. These methylated cytosines—in the long non-coding RNAs (lncRNAs) HOTAIR and XIST—could also be important for their functions.
Methylated cytosines in DNA are old news, and we now know that rRNAs and tRNAs also can get methylated. But not much is known about methylation of poly(A)RNAs. The first reports on methylated adenosines in these nucleic acids surface in the ‘70s, but only within the past year have researchers looked at cytosine methylation in mRNAs.
So a team from Austria and the U.S. looked at cytosine methylation in two well-studied lncRNAs—human HOTAIR and XIST—with an adapted bisulfite sequencing method. Here’s some of what they found:
- C1683 was always methylated in HOTAIR in many cell types, including cancer cells. That cytosine is in a region that interacts with a histone demethylase complex.
- Various cytosines were methylated in XIST’s A-region in about 20% of the human clones studied. (They didn’t find it in mouse cells.) The A-region has a role in inactivating one of the X chromosomes in females.
- In XIST’s 3-D structure, all of the methylated cytosines are close to each other on the external part of a helix. They found that polycomb-repressive complex 2 (PRC2) can bind to unmodified XIST, but not to methylated XIST.
“These results suggest that cytosine methylation may serve as a general strategy to regulate the function of long non-coding RNAs,” they conclude.
Read all the details at RNA Biology, April 2013.