Identification of RNA Editing Sites in Chimpanzee by Transcriptome-wide Sequencing Data
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This work was supported by grants from The National Natural Science Foundation of China (30800644), Hi-Tech Research and Development Program of China (2007AA022204) and Chinese Key Program for Drug Invention (2008ZXJ09007-001)

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    Abstract:

    RNA editing is a widespread post-transcriptional modification mechanism that alters genetic information at the RNA level by nucleotide insertions, deletions or substitutions, which can contribute to the diversification of the transcriptome and proteome. Although tens of thousands of A-to-I RNA editing events have been found in humans, there is limited knowledge of RNA editing in other nonhuman primates. For exploring the mechanism as well as potential functions of the RNA editing events in chimpanzee, we identified RNA editing sites based on chimpanzee RNA-Seq data here. By aligning between RNA-Seq data and chimpanzee genome sequences with TopHat software, all RNA-DNA mismatch sites were regarded as a candidate set. Low quality sites were filtered out by using both genome and transcriptome sequencing quality scores. The other filters containing uncertainty of sequencing at 3'-terminial positions, read coverage, SNP sites and estimated editing level were also applied on the candidate set. Statistical tests based on the Binomial distribution and Bonferroni multiple testing correction were performed on each candidate site to remove random errors between genome and transcriptome. Then, we detected tissue- and sex-specific RNA editing sites using bioinformatics approaches based on the Fisher's exact test and the Bonferroni multiple testing correction. The Two Sample Logo software was used to analyze the feature of the sequences surrounding the RNA editing site. A total of 8 334 RNA editing sites were identified in chimpanzee transcriptome and all 12 possible categories of discordances were observed. The top four distributions were A-to-G, U-to-C, G-to-A and C-to-U editing sites, which contained 1 995, 1 452, 1 293 and 1 101 sites, respectively. Forty-one editing sites alter amino acid residues, one of them creates a new stop codon which may shorten the KRT31 protein and affect its activity. Three editing sites damage the binding of microRNA potentially. Six hundred and forty and eight hundred and seventy-two RNA editing sites were identified to be tissue-specific and sex-specific respectively. The analysis of base frequencies indicated that all substitution editings have preferences for certain neighbouring nucleotides. RNA editing is widespread in chimpanzee and has important biology function. Our findings paved the way for further exploration of the mechanism of RNA editing in primates.

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WANG Duan-Qing, HE Tao, WANG Li, WANG Yu-Min, SHAO Wei-Dong. Identification of RNA Editing Sites in Chimpanzee by Transcriptome-wide Sequencing Data[J]. Progress in Biochemistry and Biophysics,2012,39(3):282-293

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History
  • Received:July 14,2011
  • Revised:October 22,2011
  • Accepted:
  • Online: November 14,2011
  • Published: March 20,2012