Noncoding regions of<i>C. elegans</i>mRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript

Wheeler, Emily C.; Washburn, Michael C.; Major, François; Rusch, Douglas B.; Hundley, Heather A.

doi:10.1080/15476286.2015.1017220

Cited by 13 publications

(16 citation statements)

References 59 publications

(84 reference statements)

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“…Thus, ADAR editing of RNA has sequence preferences, commonly referred to as nearest neighbors . Next‐generation sequencing studies have indicated that in most organisms, ADARs generally favor adenosines with a 5′ neighbor of uridine or cytidine and a 3′ neighbor of guanosine . However, there are slight differences in preferences between family members .…”

Section: Adar Recognition Of A‐to‐i Editing Substratesmentioning

confidence: 99%

“…Next‐generation sequencing studies have since revealed editing within Alu repeats located in noncoding regions of human mRNAs occurs at specific adenosines among different individuals . Furthermore, studies of 3′ UTRs in C. elegans revealed both editing patterns and that an editing event can affect the efficiency of editing at subsequent adenosines . Together, these studies suggest ADARs recognize specific adenosines in noncoding regions, indicating there may not be a difference in the mode of ADAR recognition of target adenosines between coding and noncoding regions.…”

Section: Adar Recognition Of A‐to‐i Editing Substratesmentioning

confidence: 99%

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To edit or not to edit: regulation of ADAR editing specificity and efficiency

Deffit

Hundley

2015

WIREs RNA

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Hundreds to millions of adenosine (A)-to-inosine (I) modifications are present in eukaryotic transcriptomes and play an essential role in the creation of proteomic and phenotypic diversity. As adenosine and inosine have different base-pairing properties, the functional consequences of these modifications or 'edits' include altering coding potential, splicing, and miRNA-mediated gene silencing of transcripts. However, rather than serving as a static control of gene expression, A-to-I editing provides a means to dynamically rewire the genetic code during development and in a cell-type specific manner. Interestingly, during normal development, in specific cells, and in both neuropathological diseases and cancers, the extent of RNA editing does not directly correlate with levels of the substrate mRNA or the adenosine deaminase that act on RNA (ADAR) editing enzymes, implying that cellular factors are required for spatiotemporal regulation of A-to-I editing. The factors that affect the specificity and extent of ADAR activity have been thoroughly dissected in vitro. Yet, we still lack a complete understanding of how specific ADAR family members can selectively deaminate certain adenosines while others cannot. Additionally, in the cellular environment, ADAR specificity and editing efficiency is likely to be influenced by cellular factors, which is currently an area of intense investigation. Data from many groups have suggested two main mechanisms for controlling A-to-I editing in the cell: (1) regulating ADAR accessibility to target RNAs and (2) protein-protein interactions that directly alter ADAR enzymatic activity. Recent studies suggest cis- and trans-acting RNA elements, heterodimerization and RNA-binding proteins play important roles in regulating RNA editing levels in vivo. WIREs RNA 2016, 7:113-127. doi: 10.1002/wrna.1319.

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Section: Adar Recognition Of A‐to‐i Editing Substratesmentioning

confidence: 99%

Section: Adar Recognition Of A‐to‐i Editing Substratesmentioning

confidence: 99%

To edit or not to edit: regulation of ADAR editing specificity and efficiency

Deffit

Hundley

2015

WIREs RNA

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“…ADARs prefer an adenosine, uridine or cytidine 5 ′ of the target adenosine while guanosine is favored 3 ′ to the adenosine (Lehmann and Bass 2000;Eggington et al 2011;Bahn et al 2012;Bazak et al 2014). However, editing sites with the same surrounding nucleotide context can exhibit drastically different editing levels, suggesting this is not the only determinant of editing efficiency (Kawahara et al 2008;Tian et al 2011;Wheeler et al 2015). Alternative splicing of ADAR transcripts (Lai et al 1997;Rueter et al 1999) and post-transcriptional modification (Desterro et al 2005) have both been observed to cause decreased ADAR activity.…”

Section: Introductionmentioning

confidence: 99%

“…We previously demonstrated that ADR-1 does not edit RNA, but it can function to regulate the extent to which specific adenosines are edited by ADR-2 (Washburn et al 2014). In addition, we identified a novel C. elegans editing target, the mRNA Y75B8A.8, and characterized the pattern of editing events within its 3 ′ UTR (Wheeler et al 2015). As this 3 ′ UTR contains two highly edited sites, we utilized this gene to generate a reporter system to examine cis-and trans-acting factors that affect editing efficiency in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans

Washburn

Hundley

2016

RNA

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Adenosine-to-inosine RNA editing by ADARs affects thousands of adenosines in an organism's transcriptome. However, adenosines are not edited at equal levels nor do these editing levels correlate well with ADAR expression levels. Therefore, additional mechanisms are utilized by the cell to dictate the editing efficiency at a given adenosine. To examine cis-and transacting factors that regulate A-to-I editing levels specifically in neural cells, we utilized the model organism Caenorhabditis elegans. We demonstrate that a double-stranded RNA (dsRNA) binding protein, ADR-1, inhibits editing in neurons, which is largely masked when examining editing levels from whole animals. Furthermore, expression of ADR-1 and mRNA expression of the editing target can act synergistically to regulate editing efficiency. In addition, we identify a dsRNA region within the Y75B8A.8 3 ′ UTR that acts as a cis-regulatory element by enhancing ADR-2 editing efficiency. Together, this work identifies mechanisms that regulate editing efficiency of noncoding A-to-I editing sites, which comprise the largest class of ADAR targets.

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Revealing the hidden RBP–RNA interactions with RNA modification enzyme‐based strategies

Jin,

Li,

Jia

et al. 2024

WIREs RNA

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RNA‐binding proteins (RBPs) are powerful and versatile regulators in living creatures, playing fundamental roles in organismal development, metabolism, and various diseases by the regulation of gene expression at multiple levels. The requirements of deep research on RBP function have promoted the rapid development of RBP–RNA interplay detection methods. Recently, the detection method of fusing RNA modification enzymes (RME) with RBP of interest has become a hot topic. Here, we reviewed RNA modification enzymes in adenosine deaminases that act on RNA (ADAR), terminal nucleotidyl transferase (TENT), and activation‐induced cytosine deaminase/ApoB mRNA editing enzyme catalytic polypeptide‐like (AID/APOBEC) protein family, regarding the biological function, biochemical activity, and substrate specificity originated from enzyme selves, their domains and partner proteins. In addition, we discussed the RME activity screening system, and the RME mutations with engineered enzyme activity. Furthermore, we provided a systematic overview of the basic principles, advantages, disadvantages, and applications of the RME‐based and cross‐linking and immunopurification (CLIP)‐based RBP target profiling strategies, including targets of RNA‐binding proteins identified by editing (TRIBE), RNA tagging, surveying targets by APOBEC‐mediated profiling (STAMP), CLIP‐seq, and their derivative technology.This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition RNA Processing > RNA Editing and Modification

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Noncoding regions ofC. elegansmRNA undergo selective adenosine to inosine deamination and contain a small number of editing sites per transcript

Cited by 13 publications

References 59 publications

To edit or not to edit: regulation of ADAR editing specificity and efficiency

To edit or not to edit: regulation of ADAR editing specificity and efficiency

Trans and cis factors affecting A-to-I RNA editing efficiency of a noncoding editing target in C. elegans

Revealing the hidden RBP–RNA interactions with RNA modification enzyme‐based strategies

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