A n A ly s i s RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ~767 million sequencing reads from poly(A) + , poly(A) − and small RNA samples. We developed a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most changes (~93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential link between RNA editing and miRNAmediated regulation. Our approach facilitates large-scale studies to profile and compare editomes across a wide range of samples.RNA editing is an integral step in generating the diversity and plasticity of cellular RNA signatures. Most editing events convert A to I(G) (adenosine to inosine, which is translated as guanosine), and are catalyzed by the double-stranded RNA-specific ADAR family of proteins. On the basis of its overabundance in repetitive Alu elements and the brain transcriptome 1-3 , RNA editing has been viewed as a key determinant in primate evolution and the development of higher brain functions 4 . Many outstanding questions on the extent and consequences of RNA editing in humans remain unanswered, despite extensive documentation of edited sites through bioinformatics approaches 5-9 and the reported roles of editing in altering genetic messages and other post-transcriptional events such as RNA splicing and miRNA regulation 2,10-12 . Global and unequivocal identification of RNA editing targets represents a critical first step in further understanding this post-transcriptional modification. This calls for complete information on whole-genome and transcriptome sequences from the same individual, so as to exclude polymorphisms and mutations among populations, as well as experimental approaches with the necessary high-throughput sequencing and base resolution 13,14 . Whole-transcriptome deep-sequencing technologies (e.g., RNASeq) [15][16][17] , with their capacity to simultaneously assay the entire transcriptome, represent an excellent choice of tool in this regard. Recent studies reporting the use of target-specific RNA-Seq 4,18 , the combination of DNA capture and parallel sequencing 19 , and mRNA-Seq 20,21 to find human RNA editing sites attest to the notion that this strategy is advantageous in addressing many outstanding questions of the editing phenomenon and its implications on the transcriptome.In this study, we used RNA-Seq to identify post-transcriptional editing events. Our unbiased and in-depth approach revealed many editing sites in transcripts corresp...
Acute mountain sickness (AMS), which may progress to life-threatening high-altitude cerebral edema, is a major threat to millions of people who live in or travel to high altitude. Although studies have revealed the risk factors and pathophysiology theories of AMS, the molecular mechanisms of it do not comprehensively illustrate. Here, we used a system-level methodology, RNA sequencing, to explore the molecular mechanisms of AMS at genome-wide level in 10 individuals. After exposure to high altitude, a total of 1,164 and 1,322 differentially expressed transcripts were identified in AMS and non-AMS groups, respectively. Among them, only 328 common transcripts presented between the two groups. Immune and inflammatory responses were overrepresented in participants with AMS, but not in non-AMS individuals. Anti-inflammatory cytokine IL10 and inflammation cytokines IF17F and CCL8 exhibited significantly different genetic connectivity in AMS compared to that of non-AMS individuals based on network analysis. IL10 was downregulated and both IF17F and CCL8 were upregulated in AMS individuals. Moreover, the serum concentration of IL10 significantly decreased in AMS patients after exposure to high altitude (p = 0.001) in another population (n = 22). There was a large negative correlation between the changes in IL10 concentration, r(22) = −0.52, p = 0.013, and Lake Louise Score. Taken together, our analysis provides unprecedented characterization of AMS transcriptome and identifies that genes involved in immune and inflammatory responses were disturbed in AMS individuals by high-altitude exposure. The reduction of IL10 after exposure to high altitude was associated with AMS.
http://bioinfo.icts.hkbu.edu.hk/cmgrn; http://www.byanbioinfo.org/cmgrn CONTACT: yanbinai6017@gmail.com or junwen@hku.hk Supplementary Information: Supplementary data are available at Bioinformatics online.
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