Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila

Laurent, Georges St.; Tackett, Michael; Nechkin, Sergey; Shtokalo, Dmitry; Антонец, Денис; Savva, Yiannis A.; Maloney, Rachel; Kapranov, Philipp; Lawrence, Charles E.; Reenan, Robert A.

doi:10.1038/nsmb.2675

Cited by 131 publications

(184 citation statements)

References 45 publications

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“…It is interesting to note, however, that these results contrast sharply with those in invertebrates. In Drosophila, non-synonymous sites in coding regions are in fact over-represented (Graveley et al, 2011;St Laurent et al, 2013). In squid, the same is true (Alon et al, 2015).…”

Section: Cephalopod Rna Editing Breaks the Rulesmentioning

confidence: 53%

“…Recent advances in high-throughput DNA sequencing technologies have enabled transcriptome-wide tabulations of RNA editing events. Current estimates suggest that there may be more than a million editing sites in the human transcriptome, but almost all of them are in transcribed repetitive elements (Bazak et al, 2014;Carmi et al, 2011a,b;Eisenberg et al, 2005;Li et al, 2009;PazYaacov et al, 2010;Porath et al, 2014;Ramaswami et al, 2012;St Laurent et al, 2013). The genomes of humans and other primates are full of repeats.…”

Section: Adars Do Much More Than Alter Codonsmentioning

confidence: 99%

“…Because of the neighboring residue preferences for ADARs, this bias is even stronger. In both cephalopods and Drosophila, RNA editing creates many glycines, valines and alanines (St Laurent et al, 2013;Alon et al, 2015). Many years ago, George Somero and colleagues, while comparing metabolic enzymes from organisms that inhabit different thermal environments, hypothesized a good reason for these changes (Fields et al, 2002;Fields and Somero, 1998;Hochachka and Somero, 1968;Low et al, 1973;Low and Somero, 1974;Somero, 1975): the substitution of small amino acids at hinge regions within proteins tends to reduce activation energy barriers for enzymatic reactions.…”

Section: Cephalopod Rna Editing Breaks the Rulesmentioning

confidence: 99%

“…In Drosophila melanogaster, comparatively more recoding sites have been identified but they are still rare among messages. An Encode consortium effort (Graveley et al, 2011) and a subsequent study using a novel single-molecule sequencing pipeline (St Laurent et al, 2013) discovered 630 and 645 recoding sites, respectively. In both studies, recoding sites are enriched in mRNAs encoding proteins with neuronal functions.…”

Section: Adars Do Much More Than Alter Codonsmentioning

confidence: 99%

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The emerging role of RNA editing in plasticity

Rosenthal¹

2015

Journal of Experimental Biology

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All true metazoans modify their RNAs by converting specific adenosine residues to inosine. Because inosine binds to cytosine, it is a biological mimic for guanosine. This subtle change, termed RNA editing, can have diverse effects on various RNA-mediated cellular pathways, including RNA interference, innate immunity, retrotransposon defense and messenger RNA recoding. Because RNA editing can be regulated, it is an ideal tool for increasing genetic diversity, adaptation and environmental acclimation. This review will cover the following themes related to RNA editing: (1) how it is used to modify different cellular RNAs, (2) how frequently it is used by different organisms to recode mRNA, (3) how specific recoding events regulate protein function, (4) how it is used in adaptation and (5) emerging evidence that it can be used for acclimation. Organismal biologists with an interest in adaptation and acclimation, but with little knowledge of RNA editing, are the intended audience.

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Section: Cephalopod Rna Editing Breaks the Rulesmentioning

confidence: 53%

Section: Adars Do Much More Than Alter Codonsmentioning

confidence: 99%

Section: Cephalopod Rna Editing Breaks the Rulesmentioning

confidence: 99%

Section: Adars Do Much More Than Alter Codonsmentioning

confidence: 99%

See 2 more Smart Citations

The emerging role of RNA editing in plasticity

Rosenthal¹

2015

Journal of Experimental Biology

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“…Experiments on unidentified iGluRs in cultured Drosophila myotubes revealed a high Ca 2+ permeability, P Ca /P Na 9.6 (46), comparable to the value for NMDA receptors, P Ca /P Na 10.6 (47), and much higher than that for vertebrate AMPA and kainate receptors, P Ca /P Na 1.2-1.4 (22,48). It is thus noteworthy that although RNA editing occurs in Drosophila and modifies Shab potassium channel inactivation (49), a genome-wide analysis by single-molecule sequencing found no evidence of editing for Drosophila NMJ iGluRs (50). As a consequence, activity-dependent Ca 2+ influx at the Drosophila NMJ is likely to play an unusually prominent role in synapse development and regulation.…”

Section: Discussionmentioning

confidence: 99%

Functional reconstitution ofDrosophila melanogasterNMJ glutamate receptors

Han

Dharkar

Mayer

et al. 2015

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

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The Drosophila larval neuromuscular junction (NMJ), at which glutamate acts as the excitatory neurotransmitter, is a widely used model for genetic analysis of synapse function and development. Despite decades of study, the inability to reconstitute NMJ glutamate receptor function using heterologous expression systems has complicated the analysis of receptor function, such that it is difficult to resolve the molecular basis for compound phenotypes observed in mutant flies. We find that Drosophila Neto functions as an essential component required for the function of NMJ glutamate receptors, permitting analysis of glutamate receptor responses in Xenopus oocytes. In combination with a crystallographic analysis of the GluRIIB ligand binding domain, we use this system to characterize the subunit dependence of assembly, channel block, and ligand selectivity for Drosophila NMJ glutamate receptors.T he amino acid L-glutamate is the major neurotransmitter at vertebrate excitatory central synapses and at the neuromuscular junction (NMJ) of insects and crustaceans (1-3). Many vertebrate AMPA and kainate receptors, as well as GluRI from the worm Caenorhabditis elegans and AvGluR1 from the rotifer Adineta vaga, can form functional homomeric ion channels (1, 4, 5). In contrast, genetic studies suggest that assembly of Drosophila NMJ type A and type B glutamate receptors requires four subunits: either GluRIIA or GluRIIB, plus GluRIIC, GluRIID, and GluRIIE (6-9); both subtypes desensitize rapidly, with time constants of 18.8 and 2.0 ms, respectively (6). In flies, lack of GluRIIA and GluRIIB or any other single subunit induces embryonic paralysis. Furthermore, in the absence of GluRIIA and GluRIIB, or any other subunit, none of the remaining iGluR subunits cluster at nascent synapses, suggesting that recruitment and stabilization of iGluRs at synaptic sites requires heterotetramers. Despite a decade of work, the molecular basis for this unique profile has remained obscure. In part, this is because the reconstitution of functional glutamate receptors (iGluRs) in heterologous systems, which has been a powerful tool for analysis of receptor function in other species, has not been achieved for the Drosophila NMJ (10).We recently demonstrated that the synaptic distribution of Drosophila NMJ iGluRs requires Neto (Neuropillin and Tolloidlike), a protein essential for NMJ function (11). Neto belongs to a family of highly conserved auxiliary proteins that modulate the function of vertebrate kainate receptors (12) and C. elegans AMPA receptors (13,14). In these species Neto plays a minor role in delivery and synaptic targeting, and instead modulates receptor gating properties. In contrast, in flies Neto is absolutely required for clustering of iGluRs at the NMJ and lack of Neto induces embryonic paralysis (11). This finding may reflect a role for Neto in receptor assembly, surface expression, synaptic trafficking and stabilization, or modulation of iGluR gating. To distinguish among these possibilities, a recombinant expression system for...

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Does RNA editing compensate for Alu invasion of the primate genome?

Levanon

Eisenberg

2014

BioEssays

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One of the distinctive features of the primate genome is the Alu element, a repetitive short interspersed element, over a million highly similar copies of which account for >10% of the genome. A direct consequence of this feature is that primates' transcriptome is highly enriched in long stable dsRNA structures, the preferred target of adenosine deaminases acting on RNAs (ADARs), which are the enzymes catalyzing A-to-I RNA editing. Indeed, A-to-I editing by ADARs is extremely abundant in primates: over a hundred million editing sites exist in their genomes. However, there are few essential editing sites conserved across mammals that have maintained their editing level despite the radical change in ADAR target landscape. Here, we review and discuss the cost of having an unusual amount of dsRNA and editing in the transcriptome, as well as the opportunities it presents, which might have contributed to the accelerated evolution of the primates.

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Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in Drosophila

Cited by 131 publications

References 45 publications

The emerging role of RNA editing in plasticity

The emerging role of RNA editing in plasticity

Functional reconstitution ofDrosophila melanogasterNMJ glutamate receptors

Does RNA editing compensate for Alu invasion of the primate genome?

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