DNA is supposed to be faithfully transcribed into RNA and translated into proteins. But sometimes, changes occur to the RNA. Usually that means that an adenosine becomes inosine, which is then read as guanosine. While this increases the diversity of the transcriptome, the frequency and function of such RNA editing is not clear. Recent studies, including one that researchers from BGI-Shenzhen published in Nature Biotechnology, are finding that RNA editing may be common.
"A number of questions on RNA editing remain to be answered, such as how prevalent RNA editing is, and the detailed function and role of RNA editing in the process of post-transcriptional modification," says Zhiyu Peng, vice director of research and cooperation at BGI and the study's lead author. "To definitively and quantitatively characterize [the] RNA editome may be the first step toward answering these questions."
Peng and his collaborators used RNA sequencing to obtain deep transcriptome data from a lymphoblastoid cell line from an individual whose genome had been sequenced previously. From this, Peng says, the researchers identified more than 70,000 RNA editing sites. The team mapped the DNA and RNA reads back to the reference genome and filtered the data to account for heterozygosity, mapping errors, and sequence quality, among other possible errors.
Nearly 90 percent of editing events Peng and his colleagues uncovered were adenosine-to-guano-sine- changes. This, he says, is not surprising, as it is consistent with previous studies, adding that about 60 percent to 70 percent of the editing events they saw in the initial dataset were adenosine-to-guanosine conversions. "After filtering the data by more stringent criterions, we found the percentage of A-to-G increased," Peng says. A 2011 Science study from Mingyao Li at the University of Pennsylvania School of Medicine reported that about 23 percent of editing events were adenosine to guanosine changes, while a January Genome Research paper from the University of California, Los Angeles' Jae Hoon Bahn found that about 62 percent of RNA editing changes were adenosine to guanosine. Peng says that technical differences between the groups' approaches may contribute to the range of percentages reported.
He and his colleagues also found that a number of RNA editing sites could affect microRNAs. They found 44 editing sites in 30 mature miRNA sequences, 11 of which fall within seed regions and could affect target specificity. "These findings indicated that there was a potential connection between RNA editing and miRNA-mediated regulation," Peng says. "However, the importance of RNA editing for miRNA regulation needs to be further studied."