Functions and Mechanisms of Rna Editing

Gott, Jonatha M.; Emeson, Ronald B.

doi:10.1146/annurev.genet.34.1.499

Cited by 451 publications

(368 citation statements)

References 220 publications

Supporting

Mentioning

361

Contrasting

Unclassified

Order By: Relevance

“…RNA editing is a co-or post-transcriptional process (Gott and Emeson, 2000) that modifies the genetic information at the transcript level, either by insertion or deletion of nucleotides, or by base modification. Enzymatic base modification of RNA sequences was originally discovered in the mitochondrial RNA of trypanosomes (Turelli and Trono, 2005).…”

Section: Discussionmentioning

confidence: 99%

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

View full text Add to dashboard Cite

The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding protein involved in many processes that compose gene expression. K protein is upregulated in the malignant processes and has been shown to modulate the expression of genes involved in mitogenic responses and tumorigenesis. To explore the possibility that there are alternative isoforms of K protein expressed in colon cancer, we amplified and sequenced K protein mRNA that was isolated from colorectal cancers as well as from normal tissues surrounding the tumours. Sequencing revealed a single G-to-A base substitution at position 274 that was found in tumours and surrounding mucosa, but not in individuals that had no colorectal tumour. This substitution most likely reflects an RNA editing event because it was not found in the corresponding genomic DNAs. Sequencing of RNA from normal colonic mucosa of patients with prior resection of colorectal cancer revealed only the wild-type K protein transcript, indicating that G274A isoform is tumour related. To our knowledge, this is the first example of an RNA editing event in cancer and its surrounding tissue, a finding that may offer a new diagnostic and treatment marker.

show abstract

Section: Discussionmentioning

confidence: 99%

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

View full text Add to dashboard Cite

show abstract

“…RNA editing is a post-transcriptional process that changes the nucleotide sequence of an RNA transcript from the DNA sequence encoded by the corresponding gene 2 . Editing of mRNAs, transfer RNAs and ribosomal RNAs has been reported in bacteria to man.…”

Section: Box 1 Different Types Of Rna Editingmentioning

confidence: 99%

“…ADAT1 edits A37 (near the anticodon) of tRNA Ala , and the heterodimeric ADAT2-ADAT3 complex edits A34 at the wobble position of the anticodon of a subset of tRNAs [3][4][5]110 . ADAR genes are thought to have evolved from ADAT genes [2][3][4][5]110 . …”

mentioning

confidence: 99%

Editor meets silencer: crosstalk between RNA editing and RNA interference

Nishikura

2006

Nat Rev Mol Cell Biol

258

263

View full text Add to dashboard Cite

The most prevalent type of RNA editing is mediated by ADAR (adenosine deaminase acting on RNA) enzymes, which convert adenosines to inosines (a process known as A→I RNA editing) in double-stranded (ds)RNA substrates. A→I RNA editing was long thought to affect only selected transcripts by altering the proteins they encode. However, genome-wide screening has revealed numerous editing sites within inverted Alu repeats in introns and untranslated regions. Also, recent evidence indicates that A→I RNA editing crosstalks with RNA-interference pathways, which, like A→I RNA editing, involve dsRNAs. A→I RNA editing therefore seems to have additional functions, including the regulation of retrotransposons and gene silencing, which adds a new urgency to the challenges of fully understanding ADAR functions.An RNA transcript is subjected to various maturation processes, such as 5′ capping, splicing, 3′ processing and polyadenylation, after it is transcribed from the gene. Post-transcriptional processing of primary transcripts is essential to generate mature messenger RNAs that are ready to be translated into proteins 1 . RNA editing is a post-transcriptional-processing mechanism that results in an RNA sequence that is different from the one encoded by the genome, and thereby contributes to the diversity of gene products. There are different types of RNA-editing mechanism that either add or delete nucleotides, or that change one nucleotide into another 2 (BOX 1).The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I) in double-stranded (ds)RNAs through the action of ADAR (adenosine deaminase acting on RNA) enzymes [3][4][5] . A→I RNA editing of a short dsRNA that has formed between a coding exon and nearby intron sequences can lead to a codon change and an alteration in the protein function. However, it was recently discovered that the most frequent targets of A→I RNA editing seem to be long, but partially double-stranded, RNAs that are formed from inverted Alu repeats and long interspersed element (LINE) repeats located in introns and untranslated regions (UTRs) of mRNAs [6][7][8][9] . Global editing of non-coding RNA might control the expression of genes that harbour these repeat sequences of retrotransposon origin.Post-transcriptional gene regulation can also occur through RNA interference (RNAi), an evolutionarily conserved phenomenon that involves dsRNA molecules 10,11 . Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are non-coding RNAs that are generated by a class of RNase III ribonucleases (specifically, Dicer and Drosha). These small RNAs are incorporated into the RNA-induced silencing complex (RISC), which mediates the RNAi process [12][13][14][15][16] . The idea that the RNAi and A→I RNA editing pathways might compete for a Competing interests statement: The author declares no competing financial interests. [23][24][25] . NIH Public AccessIn this review, I discuss recent findings on new functions of A→I RNA editing in the regulation of non...

show abstract

“…There are different types of RNA-editing that either add or delete nucleotides, or that change one nucleotide into another. 15 The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine (A) residues into inosine (I). 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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Functions and Mechanisms of Rna Editing

Cited by 451 publications

References 220 publications

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

Editor meets silencer: crosstalk between RNA editing and RNA interference

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

Contact Info

Product

Resources

About