RNA editing in regulating gene expression in the brain

Jepson, James E.C.; Reenan, Robert A.

doi:10.1016/j.bbagrm.2007.11.009

Cited by 96 publications

(86 citation statements)

References 151 publications

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“…While many editing substrates are most prominently edited in the brain [23] our analysis revealed elevated levels of Flnb RNA editing in non-brain tissues. Highest rates of Flnb editing were observed in the cardiovascular and musculoskeletal systems.…”

Section: Resultsmentioning

confidence: 99%

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Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

et al. 2018

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Adenosine to inosine RNA editing in protein-coding messenger RNAs (mRNAs) potentially leads to changes in the amino acid composition of the encoded proteins. The mRNAs encoding the ubiquitously expressed actin-crosslinking proteins Filamin A and Filamin B undergo RNA editing leading to a highly conserved glutamine to arginine exchange at the identical position in either protein. Here, by targeted amplicon sequencing we analysed the RNA editing of Filamin B across several mouse tissues during post-natal development. We find highest filamin B editing levels in skeletal muscles, cartilage and bones, tissues where Filamin B function seems most important. Through the analysis of Filamin B editing in mice deficient in either ADAR1 or 2, we identified ADAR2 as the enzyme responsible for Filamin B RNA editing. We show that in neuronal tissues Filamin B editing drops in spliced transcripts indicating regulated maturation of edited transcripts. We show further that the variability of Filamin B editing across several organs correlates with its mRNA expression.

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Section: Resultsmentioning

confidence: 99%

“…The highest Flnb editing rates were detected outside the nervous system where most other protein-coding ADAR targets had been identified [23]. However, abundant editing outside the nervous system had also been found for Flna [20].…”

Section: Discussionmentioning

confidence: 99%

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

et al. 2018

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“…Of these different kinds of nuclear-encoded RNA editing, the most universal type is adenosine to inosine transition by adenosine deamination in metazoans (2). Recent reviews on RNA editing have been elaborated on the ADAR gene organization, molecular mechanism, biological significance, and evolution in chordate and invertebrate genomes (2)(3)(4)(5)(6)(7). Here, we focus on the origin and evolution of ADAR-mediated RNA editing.…”

Section: Introductionmentioning

confidence: 99%

Origins and evolution of ADAR‐mediated RNA editing

2009

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SummaryAdenosine deaminases acting on RNA (ADARs) convert adenosines to inosines in double-stranded RNA in animals. Identification of more ADAR targets and genome sequences of diverse eukaryotes present an opportunity to elucidate the origin and evolution of ADAR-mediated RNA editing. Comparative analysis of the adenosine deaminase family indicates that the first ADAR might have evolved from adenosine deaminases acting on tRNAs after the split of protozoa and metazoa. ADAR1 and ADAR2 arose by gene duplications in early metazoan evolution, 700 million years ago, while ADAR3 and TENR might originate after Urochordata-Vertebrata divergence. More ADAR or ADAR-like genes emerged in some animals (e.g., fish). Considering the constrained structure, ADAR targets are proposed to have evolved from transposable elements and repeats, random selection, and fixation, and intermolecular pairs of sense and antisense RNA. In some degree, increased ADAR-mediated gene regulation should substantially contribute to the emergence and evolution of complex metazoans, particularly the nervous system.2009 IUBMB IUBMB Life, 61(6): 572-578, 2009

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“…Inosine (I) is an abundant type of RNA modification found in the double-stranded regions of RNAs (dsRNA) of metazoans and is formed through the hydrolytic deamination of adenosines to inosines (A-to-I editing) catalyzed by adenosine deaminase that acts on RNA (ADAR) (Bass 2002). Functional ADAR is required for normal development in vertebrates (Higuchi et al 2000;Wang et al 2000;Wang et al 2004) and normal behavior in invertebrates (Jepson and Reenan 2008). A number of pathogenic mutations in ADAR (also known as ADAR1) gene are associated with dyschromatosis symmetrica hereditaria (DSH) (Tojo et al 2006;Keller et al 2008) and Aicardi-Goutieres syndrome (AGS) (Rice et al 2012).…”

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confidence: 99%

A biochemical landscape of A-to-I RNA editing in the human brain transcriptome

et al. 2014

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Inosine is an abundant RNA modification in the human transcriptome and is essential for many biological processes in modulating gene expression at the post-transcriptional level. Adenosine deaminases acting on RNA (ADARs) catalyze the hydrolytic deamination of adenosines to inosines (A-to-I editing) in double-stranded regions. We previously established a biochemical method called “inosine chemical erasing” (ICE) to directly identify inosines on RNA strands with high reliability. Here, we have applied the ICE method combined with deep sequencing (ICE-seq) to conduct an unbiased genome-wide screening of A-to-I editing sites in the transcriptome of human adult brain. Taken together with the sites identified by the conventional ICE method, we mapped 19,791 novel sites and newly found 1258 edited mRNAs, including 66 novel sites in coding regions, 41 of which cause altered amino acid assignment. ICE-seq detected novel editing sites in various repeat elements as well as in short hairpins. Gene ontology analysis revealed that these edited mRNAs are associated with transcription, energy metabolism, and neurological disorders, providing new insights into various aspects of human brain functions.

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RNA editing in regulating gene expression in the brain

Cited by 96 publications

References 151 publications

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system

Origins and evolution of ADAR‐mediated RNA editing

A biochemical landscape of A-to-I RNA editing in the human brain transcriptome

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