miRNA Editing—We Should Have Inosine This Coming

Habig, Jeffrey W.; Dale, Taraka; Bass, Brenda

doi:10.1016/j.molcel.2007.03.010

Cited by 39 publications

(22 citation statements)

References 9 publications

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“…Significantly, we note that A/I editing of non-miRNAs by the adenosine deaminase, ADAR2, has been shown to occur in the nucleolus (Vitali et al 2005), and it is known that some miRNA precursors are subject to editing (Luciano et al 2004;Blow et al 2006;Habig et al 2007;Kawahara et al 2008). miRNA editing can also interfere with processing (Yang et al 2006;Kawahara et al 2007), which conceivably could cause sequestration of unprocessed miRNA precursors in the nucleolus.…”

Section: Discussionmentioning

confidence: 69%

“…Like Drosha processing, this step is also subject to regulation . Additionally, some miRNA transcripts are also subject to A/I editing (Luciano et al 2004;Blow et al 2006;Habig et al 2007;Kawahara et al 2008), and such editing can interfere with processing (Yang et al 2006;Kawahara et al 2007). miRNAs that have been diced and assembled into an Argonaute complex then interact via short ''seed'' sequences with mRNAs in the cytoplasm to regulate translation (Du and Zamore 2005;Filipowicz et al 2008), and in some cases, miRNAs have been isolated in polysomal complexes (Kim et al 2004;see Wang et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs with a nucleolar location

Politz¹,

Hogan²,

Pederson³

2009

RNA

168

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There is increasing evidence that noncoding RNAs play a functional role in the nucleus. We previously reported that the microRNA (miRNA), miR-206, is concentrated in the nucleolus of rat myoblasts, as well as in the cytoplasm as expected. Here we have extended this finding. We show by cell/nuclear fractionation followed by microarray analysis that a number of miRNAs can be detected within the nucleolus of rat myoblasts, some of which are significantly concentrated there. Pronounced nucleolar localization is a specific phenomenon since other miRNAs are present at only very low levels in the nucleolus and occur at much higher levels in the nucleoplasm and/or the cytoplasm. We have further characterized a subset of these miRNAs using RT-qPCR and in situ hybridization, and the results suggest that some miRNAs are present in the nucleolus in precursor form while others are present as mature species. Furthermore, we have found that these miRNAs are clustered in specific sites within the nucleolus that correspond to the classical granular component. One of these miRNAs is completely homologous to a portion of a snoRNA, suggesting that it may be processed from it. In contrast, the other nucleolar-concentrated miRNAs do not show homology with any annotated rat snoRNAs and thus appear to be present in the nucleolus for other reasons, such as modification/processing, or to play roles in the late stages of ribosome biosynthesis or in nonribosomal functions that have recently been ascribed to the granular component of the nucleolus.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

MicroRNAs with a nucleolar location

Politz¹,

Hogan²,

Pederson³

2009

RNA

168

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show abstract

“…Editing can affect their processing by Drosha or Dicer but can also alter microRNA:mRNA interactions. [5][6][7][8][9] In coding regions of mRNA editing events are relatively rare. However, during the last years several evolutionary conserved adenosine to inosine editing events have been identified in coding regions.…”

Section: Introductionmentioning

confidence: 99%

Proteome diversification by adenosine to inosine RNA-editing

Pullirsch

Jantsch²

2010

RNA Biology

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“…A number of recent reports reveal that ADAR-mediated Ato-I RNA editing affects the regulation of pri-and pre-miRNA processing (Bass 2006;Yang et al 2006;Habig et al 2007;Kawahara et al 2007;Ohman 2007) and redirects the target repertoire by modifying the 5Ј-seed (Blow et al 2006;Liang and Landweber 2007). Recently, high levels of terminal U-insertion and Ainsertion were reported in mature miRNAs from a large cohort of 26 cell types (Landgraf et al 2007).…”

mentioning

confidence: 99%

Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5′-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes

Reid¹,

Nagaraja²,

Lynn³

et al. 2008

Genome Res.

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Massively parallel sequencing of millions of <30-nt RNAs expressed in mouse ovary, embryonic pancreas (E14.5), and insulin-secreting beta-cells (␤TC-3) reveals that ∼50% of the mature miRNAs representing mostly the mmu-let-7 family display internal insertion/deletions and substitutions when compared to precursor miRNA and the mouse genome reference sequences. Approximately, 12%-20% of species associated with mmu-let-7 populations exhibit sequence discrepancies that are dramatically reduced in nucleotides 3-7 (5Ј-seed) and 10-15 (cleavage and anchor sites). This observation is inconsistent with sequencing error and leads us to propose that the changes arise predominantly from post-transcriptional RNA-editing activity operating on miRNA:target mRNA complexes. Internal nucleotide modifications are most enriched at the ninth nucleotide position. A common ninth base edit of U-to-G results in a significant increase in stability of down-regulated let-7a targets in inhibin-deficient mice (Inha −/−). An excess of U-insertions (14.8%) over U-deletions (1.5%) and the presence of cleaved intermediates suggest that a mammalian TUTase (terminal uridylyl transferase) mediated dUTP-dependent U-insertion/U-deletion cycle may be a possible mechanism. We speculate that mRNA target site-directed editing of mmu-let-7a duplex-bulges stabilizes "loose" miRNA:mRNA target associations and functions to expand the target repertoire and/or enhance mRNA decay over translational repression. Our results also demonstrate that the systematic study of sequence variation within specific RNA classes in a given cell type from millions of sequences generated by next-generation sequencing (NGS) technologies ("intranomics") can be used broadly to infer functional constraints on specific parts of completely uncharacterized RNAs.

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miRNA Editing—We Should Have Inosine This Coming

Abstract: In a recent issue of Science, Nishikura and colleagues provide the first evidence that editing of a microRNA (miRNA) precursor by ADARs can modulate the target specificity of the mature miRNA (Kawahara et al., 2007).

Cited by 39 publications

References 9 publications

MicroRNAs with a nucleolar location

MicroRNAs with a nucleolar location

Proteome diversification by adenosine to inosine RNA-editing

Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5′-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes

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