Recognition of the pre-miRNA structure by Drosophila Dicer-1

Tsutsumi, Akihisa; Kawamata, Tomoko; Izumi, Natsuko; Seitz, Hervé; Tomari, Yukihide

doi:10.1038/nsmb.2125

Cited by 166 publications

(183 citation statements)

References 52 publications

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“…5 The discrepancies in the above, reported substrate preferences of hDicer and Dcr-1 may be due to genuine differences between the two enzymes, different assay conditions, and/or different substrates used in the studies. Previous work examined a small number of arbitrarily selected pre-miRNAs and their mutants as Dicer substrates (e.g., Ma et al 2008;Chakravarthy et al 2010;Zhang and Zeng 2010;Park et al 2011;Starega-Roslan et al 2011;Tsutsumi et al 2011). The human genome encodes hundreds of miRNA genes, and the predicted pre-miRNAs vary greatly in the end structure, stability and length of the duplex region, and size of the terminal loop.…”

Section: Introductionmentioning

confidence: 99%

“…Drosophila melanogaster expresses two Dicer isoforms, with Dicer-1 (Dcr-1) being responsible for the processing of pre-miRNAs, and Dicer-2 for long dsRNAs (Lee et al 2004). Tsutsumi et al (2011) reported that Dcr-1 selects the correct substrates by measuring the distance between the terminal loop and the 2-nt 39 overhang of a pre-miRNA. Extending the stem region or reducing the loop size compromised the processing by Dcr-1, seemingly consistent with the findings with hDicer (Ma et al 2008;Chakravarthy et al 2010;Zhang and Zeng 2010), even though the same study also showed that hDicer did not discriminate against such different RNA substrates (Tsutsumi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

“…Tsutsumi et al (2011) reported that Dcr-1 selects the correct substrates by measuring the distance between the terminal loop and the 2-nt 39 overhang of a pre-miRNA. Extending the stem region or reducing the loop size compromised the processing by Dcr-1, seemingly consistent with the findings with hDicer (Ma et al 2008;Chakravarthy et al 2010;Zhang and Zeng 2010), even though the same study also showed that hDicer did not discriminate against such different RNA substrates (Tsutsumi et al 2011). In addition, while Dcr-1's substrate binding affinity, as measured by gel shift assays, primarily determines RNA cleavage efficiencies (Tsutsumi et al 2011), Vermeulen et al (2005) and Chakravarthy et al (2010) showed that differences in RNA cleavage by hDicer were not simply a consequence of substrate binding.…”

Section: Introductionmentioning

confidence: 99%

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A comprehensive analysis of precursor microRNA cleavage by human Dicer

Feng

Zhang

Graves

et al. 2012

RNA

102

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Dicer cleaves double-stranded RNAs (dsRNAs) or precursor microRNAs (pre-miRNAs) to yield~22-nt RNA duplexes. The premiRNA structure requirement for human Dicer activity is incompletely understood. By large-scale in vitro dicing assays and mutagenesis studies, we showed that human Dicer cleaves most, although not all, of the 161 tested human pre-miRNAs efficiently. The stable association of RNAs with Dicer, as examined by gel shift assays, appears important but is not sufficient for cleavage. Human Dicer tolerates remarkable structural variation in its pre-miRNA substrates, although the dsRNA feature in the stem region and the 2-nt 39-overhang structure in a pre-miRNA contribute to its binding and cleavage by Dicer, and a large terminal loop further enhances pre-miRNA cleavage. Dicer binding protects the terminal loop from digestion by S1 nuclease, suggesting that Dicer interacts directly with the terminal loop region.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A comprehensive analysis of precursor microRNA cleavage by human Dicer

Feng

Zhang

Graves

et al. 2012

RNA

102

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“…Following export into the cytoplasm, pre-miRNA are cleaved by Dicer-1 to generate mature miRNA, which are then loaded onto an Ago1-dependent RNA-induced silencing complex (RISC) [56][57][58] . As in mammals, Drosophila Ars2 (dArs2) interacts with the CBC and Microprocessor, and is required for pri-miRNA processing and stability [49] .…”

Section: Ars2/serrate and Microrna Biogenesismentioning

confidence: 99%

The Diverse Requirements of ARS2 in nuclear cap-binding complex-dependent RNA Processing

O’Sullivan

Howard

2016

RNA Dis

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ARS2 is a stable component of the nuclear cap-binding complex (CBC) and is critical for RNA Polymerase II transcript processing. Moreover, ARS2, and its orthologue SERRATE in plants, has been implicated in having a role in most established CBC-dependent functions. This review will provide insight into the functions of ARS2/SERRATE in numerous RNA Polymerase II transcript processing events, which happen co-transcriptionally from initiation to termination, and post-transcriptionally during maturation and export into the cytoplasm. Additionally, we will discuss what is known regarding ARS2/SERRATE structure in plants and in mammals.

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“…In its native conformation, the region of the sponge LSU from which REm-1 derives does not form the type of secondary structure required for recognition by the canonical miRNA biogenesis machinery , Zeng et al 2005, Han et al 2006, Tsutsumi et al 2011. Furthermore, secondary structure analysis of the regions flanking REm-1 shows that the formation of such a structure is unlikely even from a fragmented LSU (Figure 5.3).…”

Section: Biogenesis Of Rem-1mentioning

confidence: 99%

RNA interference in early branching metazoans

Calcino¹

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The RNA interference (RNAi) repertoire of metazoans is principally composed of three independent but related systems -endogenous small interfering RNAs (endosiRNAs), micro RNAs (miRNAs) and Piwi-interacting RNAs (piRNAs). Although the endosiRNA pathway has been demonstrated in all five eukaryotic supergroups, the miRNA and piRNA pathways of metazoans likely evolved subsequent to metazoan divergence from other eukaryotes. These innovations evolved in a 100-200 million year period between the emergence of animal multicellularity and the divergence of the sponges. It is not yet known if the organisation and function of these systems, as characterised in bilaterian model species (vertebrates, Drosophila and C. elegans), is shared between early branching phyla (Porifera, Ctenophora, Cnidaria and Placozoa) and bilaterians. Preliminary evidence is mixed with commonalities like the existence of 'ping-pong' piRNA biogenesis in sponges and cnidarians contrasted with the lack of sequence and secondary structure homology of miRNAs between sponges and bilaterians.This thesis focuses on the RNAi systems of three early branching metazoan phyla that represent critical branches in early animal evolution (ie. Porifera, Ctenophora and Cnidaria). As no such tool was available, I developed a bioinformatic pipeline to annotate the RNAi components of mapped small RNA libraries from the demosponge Amphimedon queenslandica, the ctenophore Mnemiopsis leidyi and the cnidarian Nematostella vectensis. Detailed in Chapter 2, this pipeline, named RNAiTool, clusters mapped small RNAs from high-throughput sequencing data and then annotates those clusters based on a simple set of criteria, primarily focused on the read-length of the constituent small RNAs.RNAiTool was also used in the annotation of small RNA datasets from the well-studied bilaterian Drosophila melanogaster, providing a point of comparison for the less wellunderstood non-bilaterian species. As well as interrogating individual datasets, RNAiTool can be used to compare the expression dynamics of endo-siRNA and piRNA cluster between datasets. Although it was used here to investigate the expression dynamics of endo-siRNA and piRNA cluster through development, RNAiTool can be used to assess the expression dynamics of clusters between any test and control datasets.The second major innovation presented in this thesis is the introduction of the uniformity index. This property of small RNA clusters describes the uniformity of small RNA coverage across the length of that cluster. This simple index provides a rapid method 3 for the identification of potential miRNAs and other highly expressed small RNA producing loci from large pools of small RNA clusters. This thesis takes the first steps towards an understanding of the evolution and function of RNAi systems in early branching metazoans, in particular the demosponge A.queenslandica. It is hoped that the framework for RNAi annotation developed here will prove useful for other studies of emerging model RNAi systems. 4

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Recognition of the pre-miRNA structure by Drosophila Dicer-1

Cited by 166 publications

References 52 publications

A comprehensive analysis of precursor microRNA cleavage by human Dicer

A comprehensive analysis of precursor microRNA cleavage by human Dicer

The Diverse Requirements of ARS2 in nuclear cap-binding complex-dependent RNA Processing

RNA interference in early branching metazoans

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Recognition of the pre-miRNA structure by Drosophila Dicer-1

Cited by 166 publications

References 52 publications

A comprehensive analysis of precursor microRNA cleavage by human Dicer

A comprehensive analysis of precursor microRNA cleavage by human Dicer

The Diverse Requirements of ARS2 in nuclear cap-binding complex-dependent RNA Processing

﻿RNA interference in early branching metazoans

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RNA interference in early branching metazoans