Widespread RNA and DNA sequence differences in the human transcriptome

Abstract

The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites were found in multiple individuals and in different cell types, including primary skin cells and brain tissues. Using mass spectrometry, we detected peptides that are translated from the discordant RNA sequences and thus do not correspond exactly to the DNA sequences. These widespread RNA-DNA differences in the human transcriptome provide a yet unexplored aspect of genome variation.

Fig. 1

Characteristics of RDD sites. (A) Frequency of the 12 categories of RNA-DNA differences identified in B cells of 27 normal individuals. (B) Number of RNA editing or RDD events in 27 normal individuals. (C) Bimodal distribution of the levels of 28,766 RNA editing or RDD events.

Fig. 2

Identification of peptides coded by both RNA and DNA sequences. (A) The RNA form of a RDD leads to loss of a stop codon in RPL28 and extension of 55 amino acids. Peptides detected by mass spectrometry are shown in red. Extended protein sequence due to RDD is underlined. (B and C) Tandem mass spectrometry (MS-MS) data confirm the detection of peptides encoded by the RDD-containing RPL28 mRNA. The representative spectra of one peptide (SLIGTASEPR) from ovarian cancer cells (B) and cultured B cells (C) are shown.