Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Bramsen, Jesper B.; Berthou, Christian; Panitz, Frank; Holm, Ida E.; Öhman, Marie; Kjems, Jørgen

doi:10.4161/rna.21082

Cited by 37 publications

(37 citation statements)

References 43 publications

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“…This hypothesis is in agreement with previous studies on the coupling of editing sites within short imperfect duplexes present in coding regions of mRNA. 45,54 However, in contrast to those studies, the positively correlated sites we observe in 3 0 UTRs do not occur in regular intervals along the duplex. Therefore, it is unlikely that cooperative interactions occur between ADAR molecules binding sequentially along the RNA.…”

Section: Discussioncontrasting

confidence: 99%

“…Multiple studies characterizing editing events in the coding and noncoding regions of human mRNAs have also previously detected these long-range positive correlations, however, the mechanism of ADAR recognition that resulted in these coupled editing events was unclear. 44,54,57 Our ability to analyze the editing pattern across the 3 0 UTR revealed that although the overall co-occurrence of editing sites that are separated by multiple helical turns is positively correlated, when focusing on transcripts that contain only 2 editing events, these distant adenosines co-occur less than expected (dice coefficient of ¡0.09 for nucleotides 95 and 178 in syntaxin). This data suggest that there are certain preferences to the order in which multiple editing events occur within the 3 0 UTRs.…”

Section: Discussionmentioning

confidence: 98%

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

et al. 2015

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ADARs (Adenosine deaminases that act on RNA) "edit" RNA by converting adenosines to inosines within doublestranded regions. The primary targets of ADARs are long duplexes present within noncoding regions of mRNAs, such as introns and 3 0 untranslated regions (UTRs). Because adenosine and inosine have different base-pairing properties, editing within these regions can alter splicing and recognition by small RNAs. However, despite numerous studies identifying multiple editing sites in these genomic regions, little is known about the extent to which editing sites cooccur on individual transcripts or the functional output of these combinatorial editing events. To begin to address these questions, we performed an ultra-deep sequencing analysis of 4 Caenorhabditis elegans 3 0 UTRs that are known ADAR targets. Synchronous editing events were determined for the long duplexes in vivo. Furthermore, the validity of each editing event was confirmed by sequencing the same regions of mRNA from worms that lack A-to-I editing. This analysis identified a large number of editing sites that can occur within each 3 0 UTR, but interestingly, each individual transcript contained only a small fraction of these A-to-I editing events. In addition, editing patterns were not random, indicating that an editing event can affect the efficiency of editing at subsequent adenosines. Furthermore, we identified specific sites that can be both positively and negatively correlated with additional sites leading to mutually exclusive editing patterns. These results suggest that editing in noncoding regions is selective and hyper-editing of cellular RNAs is rare.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%

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

et al. 2015

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“…Previous studies have shown a gradual increase of A-to-I editing levels for protein-coding transcripts during mammalian neuronal development [26,27] in the presence of constant protein levels of ADAR1 and ADAR2 [28]. Recently, it was shown that in developing mouse neurons increased nuclear localization of ADAR2 might contribute to this phenomenon [29] together with protein modifications on ADARs and regulatory factors [30,31].…”

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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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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“…GluAs that include the R-type GluA2 subunit lack Ca 2+ permeability (13,39). In very early development, most mammalian GluAs are Ca 2+ -permeable GluAs (Ca-P GluAs), but the Ca 2+ -impermeable GluAs (Ca-I GluAs) population increases rapidly by birth, due to intensive Q/R RNA editing of the GluA2 subunit (40)(41)(42)(43)(44). Defects in this process cause serious problems (45)(46)(47)(48)(49).…”

Section: Resultsmentioning

confidence: 99%

AMPA glutamate receptors are required for sensory-organ formation and morphogenesis in the basal chordate

Hirai

Hotta

Kubo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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AMPA-type glutamate receptors (GluAs) mediate fast excitatory transmission in the vertebrate central nervous system (CNS), and their function has been extensively studied in the mature mammalian brain. However, GluA expression begins very early in developing embryos, suggesting that they may also have unidentified developmental roles. Here, we identify developmental roles for GluAs in the ascidian Ciona intestinalis. Mammals express Ca2+-permeable GluAs (Ca-P GluAs) and Ca2+-impermeable GluAs (Ca-I GluAs) by combining subunits derived from four genes. In contrast, ascidians have a single gluA gene. Taking advantage of the simple genomic GluA organization in ascidians, we knocked down (KD) GluAs in Ciona and observed severe impairments in formation of the ocellus, a photoreceptive organ used during the swimming stage, and in resorption of the tail and body axis rotation during metamorphosis to the adult stage. These defects could be rescued by injection of KD-resistant GluAs. GluA KD phenotypes could also be reproduced by expressing a GluA mutant that dominantly inhibits glutamate-evoked currents. These results suggest that, in addition to their role in synaptic communication in mature animals, GluAs also have critical developmental functions.

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Spatio-temporal regulation of ADAR editing during development in porcine neural tissues

Cited by 37 publications

References 43 publications

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

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

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

AMPA glutamate receptors are required for sensory-organ formation and morphogenesis in the basal chordate

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