Screening of human SNP database identifies recoding sites of A-to-I RNA editing

Abstract

Single nucleotide polymorphisms (SNPs) are DNA sequence variations that can affect the expression or function of genes. As a result, they may lead to phenotypic differences between individuals, such as susceptibility to disease, response to medications, and disease progression. Millions of SNPs have been mapped within the human genome providing a rich resource for genetic variation studies. Adenosine-to-inosine RNA editing also leads to the production of RNA and protein sequence variants, but it acts on the level of primary gene transcripts. Sequence variations due to RNA editing may be misannotated as SNPs when relying solely on expressed sequence data instead of genomic material. In this study, we screened the human SNP database for potential cases of A-to-I RNA editing that cause amino acid changes in the encoded protein. Our search strategy applies five molecular features to score candidate sites. It identifies all previously known cases of editing present in the SNP database and successfully uncovers novel, bona fide targets of adenosine deamination editing. Our approach sets the stage for effective and comprehensive genome-wide screens for A-to-I editing targets.

Proteome diversification by adenosine to inosine RNA-editing

“…11 Additional targets for RNA editing in coding regions were identified by different screens over the last years. 2,11,12,44,45 In agreement with an expected role for editing in brain function and evolution many of these editing sites were found in receptors, ion channels and proteins involved in synapse function, trafficking or membrane organization. 11 The novel targets CyFip2 (Pir121), Filamin A (Flna) and Filamin B (Flnb) are involved in different steps of actin reorganization (Fig.…”

“…[1][2][3][4][44][45][46] Most of the predicted editing sites are localized in non-coding regions. Especially the infiltration of the primate genome with Alu elements seems to have led to high editing rates in these elements.…”

Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

“…The Igfbp7 B site 28 is clearly the principal site in this amplicon with 45.6% editing. The same is evident for the Grik2 Q/R site, which has the most pronounced singular editing at 32.1%.…”

Enigmatic In Vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome

“…In particular, several methodical prospective surveys of mRNA editing in the human/mammalian transcriptome have strongly suggested that the scale of mRNA editing in the human transcriptome has been seriously underestimated [Blow et al, 2004;Furey et al, 2004;Levanon and Eisenberg, 2006;Gommans et al, 2008]. It is unlikely to be a simple coincidence that the putative example(s) of mRNA editing reported here occurred in an X-linked gene since the hemizygosity of the male patients would have clearly been expected to preclude any signal emanating from the presence of a wild-type IDS sequence, either at the cDNA or the genomic level, at least for the two patients with an inherited IDS gene lesion.…”