RNA Editing of a<i>Drosophila</i>Sodium Channel Gene

Hanrahan, Christopher J.; Palladino, Michael J.; Bonneau, Laurie J.; Reenan, Robert A.

doi:10.1111/j.1749-6632.1999.tb11273.x

Cited by 23 publications

(11 citation statements)

References 52 publications

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“…16,17 A limited number of gene transcripts (B30), mostly those that encode channels and neurotransmitter receptors (for example, mammalian glutamate receptors, 5-HT 2C R, potassium channel Kv1.1, and Drosophila melanogaster sodium channel), have been identified to date. [18][19][20][21] When editing occurs within a coding region, it has the potential to alter codon specificity because the ribosome reads inosine as guanosine (G) resulting in altered amino-acid sequence and potentially protein function. In most cases, edited and unedited versions of a given receptor/channel coexist expanding the functional range of the receptor population.…”

Section: Introductionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

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Suicide is a major public health problem with B1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2C R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.

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Section: Introductionmentioning

confidence: 99%

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

et al. 2007

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“…This was the first gene of the ADAR family identified in Drosophila and we considered it a candidate enzyme for catalyzing the proposed editing events in the cac and para premRNAs (18,36,44). Since the sequence of the encoded deaminase domain resembles vertebrate ADAR2 more than yeast Tad1p, we initially considered the possibility that the ORF was the 3Ј end of a longer mRNA that would also encode dsRNAbinding domains.…”

Section: Resultsmentioning

confidence: 99%

“…An ADAR-like gene (N35H14) with two dsRNA-binding domains has been sequenced by the European Drosophila Genome Project and independently cloned from Drosophila (R. Reenan, personal communication). The protein encoded by this gene converts adenosine to inosine in dsRNA substrates (M. O'Connell and R. Reenan, unpublished results) and is a strong candidate for catalyzing editing in the cac and para pre-mRNAs (18,36,44).…”

Section: Discussionmentioning

confidence: 99%

“…Editing of mRNAs has been proposed to occur in Drosophila, based on the detection of variant cDNAs having adenosine-to-guanosine substitutions in mRNAs encoded by the 4f-rnp gene (37), the cacophony (cac) gene (36,44), and the paralytic (para) gene (18). We describe here the cloning and characterization of a gene encoding an adenosine deaminase from D. melanogaster that is similar to vertebrate ADARs but lacks dsRNA-binding domains.…”

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confidence: 99%

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The Properties of a tRNA-Specific Adenosine Deaminase from Drosophila melanogaster Support an Evolutionary Link between Pre-mRNA Editing and tRNA Modification

Keegan

Gerber

Brindle

et al. 2000

Molecular and Cellular Biology

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Pre-mRNA editing involving the conversion of adenosine to inosine is mediated by adenosine deaminases that act on RNA (ADAR1 and ADAR2). ADARs contain multiple double-stranded RNA(dsRNA)-binding domains in addition to an adenosine deaminase domain. An adenosine deaminase acting on tRNAs, scTad1p (also known as scADAT1), cloned from Saccharomyces cerevisiae has a deaminase domain related to the ADARs but lacks dsRNA-binding domains. We have identified a gene homologous to scADAT1 in the region of Drosophila melanogaster Adh chromosome II. Recombinant Drosophila ADAT1 (dADAT1) has been expressed in the yeast Pichia pastoris and purified. The enzyme has no activity on dsRNA substrates but is a tRNA deaminase with specificity for adenosine 37 of insect alanine tRNA. dADAT1 shows greater similarity to vertebrate ADARs than to yeast Tad1p, supporting the hypothesis of a common evolutionary origin for ADARs and ADATs. dAdat1 transcripts are maternally supplied in the egg. Zygotic expression is widespread initially and later concentrates in the central nervous system. Adenosine and cytosine have exocyclic amino groups that participate in Watson-Crick base pairing during transcription and translation. RNA editing enzymes have been discovered that deaminate specific adenosine residues to inosine (4, 32, 38, 40) or specific cytosine residues to uridine in RNA molecules (11,39). This can result in the incorporation of different amino acids at edited positions or the formation of a smaller protein due to the generation of a stop codon. Two closely related adenosine deaminases acting on RNA (ADARs) have been identified in vertebrates (3) that catalyze the deamination of specific adenosine residues to inosine in pre-mRNAs (for a review, see reference 22). These enzymes have homologous adenosine deaminase domains (32) and also contain multiple double-stranded RNA(dsRNA)-binding domains (47). ADARs recognize and deaminate specific adenosines within exons that form duplexes with flanking intronic sequences in pre-mRNA (20, 32). ADAR activity is ubiquitous and has been found in all metazoans tested and in most tissues (52). The abundance of inosine in polyA ϩ RNA has been estimated to be 1 in 17,000 nucleotides in brain and less in other mammalian tissues, correlating with ADAR expression levels (35). Inosine in edited transcripts directs the incorporation of cytosine during firststrand synthesis of cDNA (5), and RNA editing events have usually been identified in cDNA sequences in which guanosine replaces a genomically encoded adenosine (8, 45). Pre-mRNAs encoding subunits of the glutamate-gated ion channels (for a review, see reference 42) and the G protein-coupled serotonin 2C receptor (8) undergo RNA editing of their sequences by this mechanism. Proteins encoded by edited mRNAs often have functional properties that differ from the genomically encoded versions.

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“…In two species of Drosophila, transcripts from the Para locus, which encodes the major brain Na channel, are edited [132,133]. In addtion, a Drosophila Ca 2+ channel [134] and a glutamate-gated Clchannel [135] are also edited.…”

Section: Rna Editing In Loligomentioning

confidence: 99%

Identified Ion Channels in the Squid Nervous System

Rosenthal

Gilly²

2003

Neurosignals

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Our modern understanding of channels as discrete voltage-sensitive and ion-selective entities comes largely from a series of classical studies using the squid giant axon. This system has also been critical for understanding how transporters and synaptic transmission operate. This review outlines attempts to assign molecular identities to the extensively studied physiological properties of this system. As it turns out, this is no simple task. Molecular candidates for voltage-gated Na⁺, K⁺, and Ca²⁺ channels, as well as ion transporters have been isolated from the squid nervous system. Both physiological and molecular approaches have been used to equate these cloned gene products with their native counterparts. In the case of the delayed rectifier K⁺ conductance, the most thoroughly studied example, two major issues further complicate the equation. First, the ability of K⁺ channel monomers to form heteromultimers with unique properties must be considered. Second, squid K⁺ channel mRNAs are extensively edited, a process that can generate a wide variety of channel proteins from a common gene. The giant axon system is beginning to play an important role in understanding the biological relevance of this latter process.

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RNA Editing of aDrosophilaSodium Channel Gene

Cited by 23 publications

References 52 publications

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

The Properties of a tRNA-Specific Adenosine Deaminase from Drosophila melanogaster Support an Evolutionary Link between Pre-mRNA Editing and tRNA Modification

Identified Ion Channels in the Squid Nervous System

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