REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments

Abstract

RNA editing is a relevant epitranscriptome phenomenon able to increase the transcriptome and proteome diversity of eukaryotic organisms. ADAR mediated RNA editing is widespread in humans in which millions of A-to-I changes modify thousands of primary transcripts. RNA editing has pivotal roles in the regulation of gene expression or modulation of the innate immune response or functioning of several neurotransmitter receptors. Massive transcriptome sequencing has fostered the research in this field. Nonetheless, different aspects of the RNA editing biology are still unknown and need to be elucidated. To support the study of A-to-I RNA editing we have updated our REDIportal catalogue raising its content to about 16 millions of events detected in 9642 human RNAseq samples from the GTEx project by using a dedicated pipeline based on the HPC version of the REDItools software. REDIportal now allows searches at sample level, provides overviews of RNA editing profiles per each RNAseq experiment, implements a Gene View module to look at individual events in their genic context and hosts the CLAIRE database. Starting from this novel version, REDIportal will start collecting non-human RNA editing changes for comparative genomics investigations. The database is freely available at http://srv00.recas.ba.infn.it/atlas/index.html.

ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation

“…RDDpred was used for the detection of RNA-DNA differences. Training sets consisted of Mapping Error-prone Sites (negative set; http:// epigenomics.snu.ac.kr/RDDpred/prior.php) and annotated A-to-I editing sites (positive set) derived from the DARNED (Kiran et al, 2013), RADAR (Ramaswami and Li, 2014) and REDIportal (Mansi et al, 2021) databases. Murine editing sites derived from the RADAR database were converted from mm9 to mm10 assembly using LiftOver (Kuhn et al, 2013).…”

Inflammation-driven deaminase deregulation fuels human pre-leukemia stem cell evolution

“…A-to-I RNA editing signatures distinguish pre-LSCs from LSCs To further evaluate the impact of ADAR1 activation on pre-LSC evolution to LSCs, we analyzed epitranscriptomic alterations observed in our samples that are present in the REDIportal atlas of A-to-I RNA editing that contains over 16 million events curated from RNA-seq analyses derived from 549 individuals (Mansi et al, 2021). We identified known and previously unknown RNA editing events in MPN and AML (secondary and de novo) as well as normal young bone marrow (YBM) and ABM samples.…”

Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models

“…SNVs annotated using the Ensembl Variant Effect Predictor (VEP) 2 ( McLaren et al, 2016 ). SNVs that met any of the following conditions were further filtered and removed unless annotated as known RNA editing events in the REDIportal V2.0 database 3 ( Mansi et al, 2021 ): (1) located in simple repeats or homopolymer runs ≥5 nucleotides (nt); (2) located in the mitochondria; (3) located within 6 nt from splice junctions; (4) located within 1 nt from insertion-deletions (INDELs); (5) annotated as known variants in the dbSNP database; or (6) more than 90% of the samples of controls and CSDS had an AAF equal to 100% or between 40 and 60%. RNA-Seq data from another 44 adult mice (GSE89692) were used as an additional dataset to generate a list of reference G-to-A RNA editing events, and help identify high-confidence ones.…”