AsianScientist (Feb. 24, 2012) – In a new study published online in the journal Nature Biotechnology, researchers from genomics company BGI report evidence of extensive RNA editing in a human cell line.
RNA editing is a normal but not yet fully understood process in which small nucleotide changes occur after DNA has been transcribed into RNA. It is an integral step in generating diversity and plasticity of a hereditary RNA signature.
Last year, a study published in Science (Li et al. Science, 2011) reported a large number of sequence differences between mRNA and DNA in the human transcriptome.
This finding was startling because it implied that there might be a still undiscovered mechanism of ‘RNA editing’ that could disrupt the Central Dogma and affect our understanding of genetic variation.
This view, however, was strongly contested by other scientists because of technical issues and a lack of academic rigor, such as sequencing errors or mis-mapping.
In this latest study, BGI researchers used a more rigorous technique called ‘RNA-seq’ or ‘Whole Transcriptome Shotgun Sequencing’ – a revolutionary tool in transcriptomics that uses deep-sequencing technologies to identify important post-transcriptional editing events.
The team obtained whole-transcriptome data by RNA-seq from a lymphoblastoid cell line of a male Han Chinese individual (YH), whose genome sequence was previously reported as the first diploid genome of a Han Chinese.
“We used RNA-seq in the study to identify post-transcriptional editing events, and developed a computational and comprehensive pipeline to find the human RNA editing sites,” said lead author Zhiyu Peng, Vice Director of Research & Cooperation Division of BGI.
By screening RNA-DNA differences of the same individual through successive quality control filters, BGI researchers identified 22,688 RNA editing events, and found most editing events (~93 percent) convert adenosine (A) into inosine (I), which in turn is read as guanosine (G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR).
Researchers also found evidence of other types of nucleotide changes, but these were validated at lower rates.
44 editing events were also found in microRNAs, suggesting a potential connection between RNA editing and miRNA-mediated regulation.
The article can be found at: Peng Z et al. (2012) Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome.
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