C. elegans and H. sapiens mRNAs with edited 3′ UTRs are present on polysomes

Abstract

Adenosine deaminases that act on RNA (ADARs) are editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). ADARs sometimes target codons so that a single mRNA yields multiple protein isoforms. However, ADARs most often target noncoding regions of mRNAs, such as untranslated regions (UTRs). To understand the function of extensive doublestranded 39 UTR structures, and the inosines within them, we monitored the fate of reporter and endogenous mRNAs that include structured 39 UTRs in wild-type Caenorhabditis elegans and in strains with mutations in the ADAR genes. In general, we saw little effect of editing on stability or translatability of mRNA, although in one case an ADR-1 dependent effect was observed. Importantly, whereas previous studies indicate that inosine-containing RNAs are retained in the nucleus, we show that both C. elegans and Homo sapiens mRNAs with edited, structured 39 UTRs are present on translating ribosomes.

Gene regulation by SINES and inosines: biological consequences of A-to-I editing of Alu element inverted repeats

“…32 Some of these cytoplasmic RNAs show no editing in their IRAlus, while others are edited to a significant extent. 32 In agreement with our results, Hundley et al, 88 have recently reported that mRNAs with structured and edited 3'-UTRs are present on polysomes from both C. elegans and H. sapiens. Interestingly, these authors also observed little effect of editing on stability or translatability of mRNA in most of the mRNAs they checked.…”

ADAR-mediated RNA editing in non-coding RNA sequences

“…Thus ADAR-mediated RNA editing may affect the interactions between the structural RNA elements and dsR-NA binding proteins, leading to alteration of translational efficiency, initiation, and termination (Figure 3). Some research shows that the stability and translatability of mRNAs are no different between wild-type C. elegans and mutants that lack editing [70]. However, this study only monitored five edited 3′-UTRs by fusing a red fluorescent protein gene in C. elegans [70].…”

“…Some research shows that the stability and translatability of mRNAs are no different between wild-type C. elegans and mutants that lack editing [70]. However, this study only monitored five edited 3′-UTRs by fusing a red fluorescent protein gene in C. elegans [70]. In fact, many RNA editing events have been identified in UTRs, especially in mammals [23,64,74,75].…”

“…Analysis shows that nearly 300 human genes have highly edited IRAlus in their 3′-UTRs [68], indicating that perhaps more genes are regulated by nuclear retention. Additionally, studies have shown that some mRNAs with edited 3′-UTRs are present in the cytoplasm [70,71]. It appears that several mRNAs can escape from hyper-editinginduced nuclear retention.…”

Sequence based identification of RNA editing sites

“…It is yet too early to call whether any of these regulation mechanisms is as widespread as Alu editing itself. [49][50][51][52][53][54][55][56] Alu repetitive elements are unique to the primates, but the occurrence of repetitive elements in general is common to all metazoa. However, applying the same methods for editing detection to other organisms has shown that there are about 40 times less editing events in mouse as compared to the human genome.…”