Landscape of adenosine-to-inosine RNA recoding across human tissues

Abstract

RNA editing by adenosine deaminases changes the information encoded in the mRNA from its genomic blueprint. Editing of protein-coding sequences can introduce novel, functionally distinct, protein isoforms and diversify the proteome. The functional importance of a few recoding sites has been appreciated for decades. However, systematic methods to uncover these sites perform poorly, and the full repertoire of recoding in human and other mammals is unknown. Here we present a new detection approach, and analyze 9125 GTEx RNA-seq samples, to produce a highly-accurate atlas of 1517 editing sites within the coding region and their editing levels across human tissues. Single-cell RNA-seq data shows protein recoding contributes to the variability across cell subpopulations. Most highly edited sites are evolutionary conserved in non-primate mammals, attesting for adaptation. This comprehensive set can facilitate understanding of the role of recoding in human physiology and diseases.

Heterogeneity of RNA editing in mesothelioma and how RNA editing enzyme ADAR2 affects mesothelioma cell growth, response to chemotherapy and tumor microenvironment

“…S2A). Nevertheless, we observed a significant correlation between ADAR1, but not ADAR2, mRNA and protein expression and editing of AZIN1 , a target of both ADAR1 and ADAR2 (38) and one of the 8 recoding sites recently described to increase in cancer (39), in the collection of cell lines (Fig. S2B).…”

“…We further analyzed the RNA editing in a set of cell lines based on the expression level of ADAR2 protein. We chose mesothelial cells (SDM104), ADAR2 low cells (ACC Meso1, SPC111, SPC212) and ADAR2 high cells (Mero95, ONE58) and determined RNA editing levels of the codon I164V of Coatomer Protein Complex subunit α ( COPA ) mRNA, a specific ADAR2 substrate (40), also part of the 8 differentially edited sites recently described in cancer (39). We found that ADAR2 protein expression was significantly correlated to the A-to-I editing of COPA (Fig.…”

“…Stress-induced transcripts downstream of protein-coding genes have been recently described to significantly contribute to human transcriptome (72) and to maintain nuclear integrity. A recent study investigating RNA editing recoding in human tissues has demonstrated the presence of putative editing complementary sequences up to 15 kb downstream to canonical transcripts, suggesting the existence of extended UTR not included in the canonical RefSeq transcripts (39). The profile of editing in different clusters in the region 5 kb downstream of genes is similar to the editing profile of exons.…”

The most common human ADAR1p150 Zα domain mutation P193A is well tolerated in mice and does not activate the integrated stress response pathway

“…There are millions of A-to-I editing sites across all tissues within the human transcriptome, with the majority located in repetitive elements such as Alu repeats (Bazak et al, 2014; Gabay et al, 2022; Picardi et al, 2015; Tan et al, 2017). In mice there are between 50,000-150,000 editing events, also concentrated in evolutionarily related repetitive elements (SINE/LINEs) (Costa Cruz et al, 2020; Licht et al ., 2019; Pfaller et al, 2018; Pinto et al, 2014).…”

Progeria and Aging - Omics Based Comparative Analysis

“…The dataset contains RNA-Seq data of dermal fibroblasts donated by ten progeria patients and 133 "apparently healthy" individuals (aged 1 to 96 years according to their metadata) [16,17]. Their dataset is publicly available on the Gene Expression Omnibus (GEO) database [18] under accession number GSE113957 [16,17] Since its publication in November 2018, the article by Fleischer et al has been cited 37 times in PubMed (until May 2022), with 13 of the citing papers mentioning the use of the GSE113957 dataset from the Fleischer et al paper [19][20][21][22][23][24][25][26][27][28][29][30][31] (as described in Table 1). According to the publications in PubMed, the dataset alone contributed to 8 studies investigating aging [20,[22][23][24][25][26][27][28].…”