The Loop Position of shRNAs and Pre-miRNAs Is Critical for the Accuracy of Dicer Processing In Vivo

Gu, Shuo; Jin, Lan; Zhang, Yue; Huang, Yong; Zhang, Feijie; Valdmanis, Paul N.; Kay, Mark A.

doi:10.1016/j.cell.2012.09.042

Cited by 263 publications

(305 citation statements)

References 52 publications

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“…1B; Cazalla et al 2011). Nonetheless, in vitro synthesized premiR-HSUR4 is efficiently cleaved by recombinant human Dicer (Cazalla et al 2011), consistent with Dicer's versatile "counting rules" involving recognition of the 5 ′ end, the 3 ′ end, or the loop of the pre-miRNA (Park et al 2011;Gu et al 2012).…”

Section: An Unusual Integrator Cleavage In Hvs Mirna Biogenesismentioning

confidence: 59%

The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends

et al. 2015

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Herpesvirus saimiri (HVS) is an oncogenic γ-herpesvirus that produces microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins immediately downstream from viral small nuclear RNAs (snRNA). The host cell Integrator complex, which recognizes the snRNA 3 ′ end processing signal (3 ′ box), generates the 5 ′ ends of HVS pre-miRNA hairpins. Here, we identify a novel 3 ′ box-like sequence (miRNA 3 ′ box) downstream from HVS premiRNAs that is essential for miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3 ′ end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only the miRNA 3 ′ box was confirmed by coimmunoprecipitation and an in situ proximity ligation assay (PLA) that we developed to localize specific transient RNA-protein interactions inside cells. Surprisingly, in contrast to snRNA 3 ′ end processing, HVS pre-miRNA 3 ′ end processing by Integrator can be uncoupled from transcription, enabling new approaches to study Integrator enzymology.

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Section: An Unusual Integrator Cleavage In Hvs Mirna Biogenesismentioning

confidence: 59%

The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends

et al. 2015

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“…Because AgoshRNAs do not mature via Dicer, they will not compete with this miRNA biogenesis process, and AgoshRNAs seem attractive molecules to silence target genes in Dicer-deficient cells, e.g., monocytes that lack Dicer expression (Coley et al 2010). Ago2-mediated processing may also yield more precise RNA molecules, as Dicer creates imprecise ends (Gu et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…As a consequence, Dicer will ignore the 19-bp stem, whereas it would have been able to bind the 21-bp stem. As Dicer cleaves at a fixed distance from the base of the hairpin, this would obviously change the actual Dicer cleavage site, which could be probed by deep sequence analysis (Gu et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity

Herrera-Carrillo

Harwig

Liu

et al. 2014

RNA

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Recent evidence indicates the presence of alternative pathways for microRNA (miRNA) and short hairpin (shRNA) processing. Specifically, some of these molecules are refractory to Dicer-mediated processing, which allows alternative processing routes via the Ago2 endonuclease. The resulting RNA molecules differ in size and sequence and will thus trigger the silencing of different target RNAs. It is, therefore, important to understand these processing routes in mechanistic detail such that one can design exclusive RNA reagents for a specific processing route. The exact sh/miRNA properties that determine this routing toward Dicer or Ago2 are incompletely understood. The size of the base-paired stem seems an important determinant, but other RNA elements may contribute as well. In this study, we document the importance of a weak G-U or U-G base pair at the top of the hairpin stem.

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“…This indicates that the mammalian Dicer is optimized for miRNA biogenesis and several specific structural adaptations discussed below support this notion. Dicer seems to interact directly with the terminal loop region of a pre-miRNA (Feng et al, 2012;Gu et al, 2012b) while a large pre-miRNA terminal loop further enhances pre-miRNA cleavage (Feng et al, 2012). A large-scale in vitro analysis and mutagenesis study of 161 human pre-miRNAs showed that human Dicer tolerates remarkable structural variation in pre-miRNA substrates (Feng et al, 2012).…”

Section: Canonical Mirna Substratesmentioning

confidence: 99%

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

Pačes

Nič²,

Novotný³

et al. 2017

EFS3

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This report is the outcome of an EFSA procurement aiming at investigating and summarising the state of knowledge on (I) the mode-of-action of dsRNA and miRNA pathways, (II) the potential for nontarget gene regulation by dsRNA-derived siRNAs or miRNAs, (III) the determination of siRNA pools in plant tissues and the importance of individual siRNAs for silencing. The report is based on a comprehensive and systematic literature search, starting with the identification and retrieval of~190,000 publications related to the research area and further filtered down with keywords to produce focused collections used for subsequent screening of titles and abstracts. The report is comprised of an (I) Introduction to the field of small RNAs, (II) a Data and Methodologies section containing strategies used for literature search and study selection, and (III) the Results of the literature review organized according to the three main procurement tasks. The outcome of the first task reviews dsRNA and miRNA pathways in mammals (including humans), birds, fish, arthropods, annelids, molluscs, nematodes, and plants. Eight taxon-dedicated chapters are based on~1,400 cumulative references chosen from~10,000 inspected titles and abstracts. We review conserved and divergent aspects of small RNA pathways and dsRNA responses in animals and plants including structure and function of key proteins as well as four basic mechanisms: genome-encoded posttranscriptional regulations (miRNA), degradation of RNAs by short interfering RNA pools generated from long dsRNA (RNAi), transcriptional silencing, and sequence-independent responses to dsRNA. The outcome of the second task focuses on base pairing between small RNAs and their target RNAs and predictability of biological effects of small RNAs in animals and plants. The outcome of the last task reviews methodology, siRNA pools, and movement of small RNAs in plants. Potential transfer of small RNAs between species and circulating miRNAs in mammals is described in the final chapter.

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The Loop Position of shRNAs and Pre-miRNAs Is Critical for the Accuracy of Dicer Processing In Vivo

Cited by 263 publications

References 52 publications

The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends

The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends

Probing the shRNA characteristics that hinder Dicer recognition and consequently allow Ago-mediated processing and AgoshRNA activity

Literature review of baseline information to support the risk assessment of RNAi‐based GM plants

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