RNA Editing adds flavor to complexity

Abstract

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.

Unusual Noncanonical Intron Editing Is Important for tRNA Splicing in Trypanosoma brucei

“…The RNA editing repertoire includes a number of disparate mechanisms, many of which serve to alter coding capacity. These include uridine insertions and deletions in trypanosomatid mitochondria, C insertions in Physarum , nucleotide deaminations (C to U and A to I) in various coding and non-coding RNAs (including tRNAs) (Aphasizhev and Aphasizheva, 2011; Blanc and Davidson, 2010; Chateigner-Boutin and Small, 2011; Gommans, 2012; Goringer et al, 2011; Jackman and Alfonzo, 2013; Jackman et al, 2012; Mallela and Nishikura, 2012; Paris et al, 2012; Sie and Kuchka, 2012; Smith et al, 2012). All of these reactions have been extensively studied and the various editing activities reconstituted in vitro .…”

The Human Transcriptome: An Unfinished Story

“…In the RNA editing process, single nucleotide changes occur after DNA has been transcribed into RNA. The resulting RNA transcripts may produce altered proteins, or they may disrupt translation more severely [56]. Two RNA editing mechanisms are known in humans, causing two types of substitutions: adenosine to inosine, and cytosine to uracil.…”

“…Until recently considered a rare event, RNA editing is now believed to affect both coding and non-coding sequences of thousands of genes, including ncRNAs [56,62,63]. A 2011 study by Li et al .…”

RNA Editing and Drug Discovery for Cancer Therapy

“…Particularly in the nervous system, editing in non-coding regions such as microRNA and 3′ untranslated regions (UTR) of mRNAs is more frequent than in coding regions [4, 23]. Therefore, correct and regulated RNA editing is important for marinating functional nervous system and avoiding neurological diseases [8, 25]. …”

“…Although five types of RNA editing have been discovered [3], the adenosine-to-inosine (A-to-I) editing is the most common type in higher eukaryotes [4–6]. The A-to-I editing may lead to changes in amino acid type and alternative splicing [7], thereby increasing the complexity of gene expression [8]. …”