RT Journal Article
SR Electronic
T1 Genome-wide analysis of RNA sites consistently edited in human blood reveals interactions with mRNA processing genes and suggests correlations with biological and drug-related variables
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 254045
DO 10.1101/254045
A1 Edoardo Giacopuzzi
A1 Massimo Gennarelli
A1 Chiara Sacco
A1 Chiara Magri
A1 Alessandro Barbon
YR 2018
UL http://biorxiv.org/content/early/2018/07/05/254045.abstract
AB Background A-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminate Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. However, little is known about how editing process could be influenced by genetic variations, biological and environmental variables.Results We analyzed RNA editing levels in human blood using RNA-seq data from 459 healthy individuals and identified 2,079 sites consistently edited in this tissue, that we considered the most biologically relevant editing sites. As expected, analysis of gene expression revealed that ADAR is the major contributor to editing on these sites, explaining ~13% of observed variability. After removing ADAR effect, we found significant associations for 1,122 genes, mainly involved in RNA processing. These genes were significantly enriched in genes encoding proteins interacting with ADARs, including 276 potential ADARs interactors and 9 ADARs direct partners. In addition, association analysis on 28 biological and drugs intake variables revealed several factors potentially influencing RNA editing in blood, including sex, age, BMI, drugs and medications. Finally, we identified genetic loci associated to editing levels, including known ADAR eQTLs and a small region on chromosome 7, containing LOC730338 lincRNA gene.Conclusions Our data provides a detailed picture of the most relevant RNA editing events and their variability in human blood, giving interesting insights on the mechanisms behind this post-transcriptional modification and its regulation in this tissue.