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.
A-to-I RNA editing results in the conversion of single adenosines into inosines, which alters coding and non-coding sequences in RNA molecules, increasing the complexity of the transcriptome. This modification is vital in a number of brain-specific coding transcripts, where the introduced alternative amino acids impact protein function substantially. Indeed, deviations from normal editing levels have been detected in tissues from individuals affected by neurological diseases and cancer, underscoring the importance of correct and regulated editing. Since the discovery of A-to-I RNA editing, considerable effort has been made to uncover additional editing targets and analyze the subsequent functional consequences for the recoded substrates. The effects of editing on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs) or long ncRNAs are less well explored. ncRNAs act as regulators of gene expression through chromatin modification, imprinting, alternative splicing, and mRNA translation and stability. Editing has the potential to dynamically alter and diversify ncRNAs, thereby redirecting their functions. How editing intersects, interferes with, and modulates the roles of ncRNAs, possibly in response to external stimuli, therefore warrants a deeper look. This review discusses recent advances and new insights in the field.
Edited by Michael IbbaKeywords: RNA editing Inosine Adenosine deaminase acting on RNA Double-stranded RNA Complement component 1, q subcomponent-like 1 Single-nucleotide polymorphism a b s t r a c t A-to-I RNA editing can lead to recoding of pre-mRNAs with profound functional consequences for the ensuing proteins. Here we show that complement component 1, q subcomponent-like 1 (C1QL1) undergoes RNA editing in vivo causing non-synonymous amino acid substitutions in human, mouse as well as zebrafish. The major editing site had previously been annotated as a single-nucleotide polymorphism in human, but our analysis reveals that post-transcriptional modification is the cause for the sequence variation. Remarkably, although editing of C1QL1 is conserved across vertebrate species, the predicted RNA secondary structure mediating editing involves different regions in zebrafish versus mammals.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.