The Canonical RNA Interference Pathway in Animals

Nejepinska, Jana; Flemr, Matyáš; Svoboda, Petr

doi:10.1007/978-3-662-45801-3_5

Cited by 6 publications

(11 citation statements)

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“…However, it is not clear if TARBP2 stimulation could be sufficient to induce endogenous RNAi in vivo [ 9 ]. So far, the evidence for endogenous RNAi (including attempts to induce RNAi with exogenous substrates) is scarce (reviewed in detail in [ 75 , 94 ]). The only tissue type, where abundant endogenous siRNAs were found and where long dsRNA readily induces RNAi, is mouse oocytes, which express an oocyte-specific Dicer isoform lacking a part of the N-terminal helicase domain [ 26 ], thus mimicking some of the mutants tested in vitro [ 63 ].…”

Section: Substrate Processing By Mammalian Dicer Proteinsmentioning

confidence: 99%

“…In Drosophila and Caenorhabditis , RNAi functions in gene regulation, silencing of transposable elements, and antiviral defense (reviewed in [ 75 ]). In contrast, mammalian RNAi seems to be, with a notable exception of rodent oocytes, a minor pathway with limited functionality.…”

Section: Biological Roles Of Mammalian Dicers Beyond the Mirna Pathwamentioning

confidence: 99%

“…Experimental evidence suggests that endogenous RNAi might function also in some other cell types (reviewed in [ 75 ]). However, the evidence for a potential physiological role of endo-siRNAs in mammalian somatic cells is scarce at best.…”

Section: Biological Roles Of Mammalian Dicers Beyond the Mirna Pathwamentioning

confidence: 99%

“…Accordingly, the term RNAi is used here strictly for sequence-specific degradation induced by long dsRNA. During RNAi (reviewed in [ 75 ]), long dsRNA is processed by Dicer into ∼20–23-nt short interfering RNAs (siRNAs). Dicer then assists in loading siRNAs onto an Argonaute protein (AGO2 in mammals).…”

Section: Introductionmentioning

confidence: 99%

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Production of small RNAs by mammalian Dicer

Svobodová

Kubíková

Svoboda

2016

Pflugers Arch - Eur J Physiol

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MicroRNA (miRNA) and RNA interference (RNAi) pathways employ RNase III Dicer for the biogenesis of small RNAs guiding post-transcriptional repression. Requirements for Dicer activity differ in the two pathways. The biogenesis of miRNAs requires a single Dicer cleavage of a short hairpin precursor to produce a small RNA with a precisely defined sequence, while small RNAs in RNAi come from a processive cleavage of a long double-stranded RNA (dsRNA) into a pool of small RNAs with different sequences. While Dicer is generally conserved among eukaryotes, its substrate recognition, cleavage, and biological roles differ. In Metazoa, a single Dicer can function as a universal factor for RNAi and miRNA pathways or as a factor adapted specifically for one of the pathways. In this review, we focus on the structure, function, and evolution of mammalian Dicer. We discuss key structural features of Dicer and other factors defining Dicer substrate repertoire and biological functions in mammals in comparison with invertebrate models. The key for adaptation of Dicer for miRNA or RNAi pathways is the N-terminal helicase, a dynamically evolving Dicer domain. Its functionality differs between mammals and invertebrates: the mammalian Dicer is well adapted to produce miRNAs while its ability to support RNAi is limited.

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Section: Substrate Processing By Mammalian Dicer Proteinsmentioning

confidence: 99%

Section: Biological Roles Of Mammalian Dicers Beyond the Mirna Pathwamentioning

confidence: 99%

Section: Biological Roles Of Mammalian Dicers Beyond the Mirna Pathwamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Production of small RNAs by mammalian Dicer

Svobodová

Kubíková

Svoboda

2016

Pflugers Arch - Eur J Physiol

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“…However, it is not clear if TARBP2 stimulation could be sufficient to induce endogenous RNAi in vivo (Chakravarthy et al, 2010). So far, the evidence for endogenous RNAi (including attempts to induce RNAi with exogenous substrates) is scarce (reviewed in detail in Nejepinska et al, 2012a;Svoboda, 2014). The only tissue type, where abundant endogenous siRNAs are present and where long dsRNA readily induces RNAi are mouse oocytes, which express an oocyte-specific Dicer isoform lacking a part of the N-terminal helicase domain (Flemr et al, 2013), thus mimicking some of the Dicer mutants tested in vitro .…”

Section: Long Dsrna Substratesmentioning

confidence: 99%

RNAi and miRNA pathways in mammals I – molecular mechanisms

Svoboda¹

2020

Introduction to RNAi and miRNA Pathways

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RNA silencing denotes sequence-specific repression mediated by small RNAs. In mammals, there are two closely related pathways, which share several protein factors: RNA interference (RNAi) and microRNA (miRNA) pathway. The miRNA pathway regulates endogenous protein-coding gene expression. It has been implicated in many biological processes and majority of mammalian genes appear to be directly or indirectly exposed to miRNA-mediated regulations. RNAi generally serves as a form of innate immunity targeting viruses and mobile elements, although it occasionally also acquired function in protein-coding gene regulation. The function of RNAi in mammals is still poorly understood but it is clear that proteins supporting RNAi are also involved in miRNA biogenesis and function. Because of the volume of information, the review of mammalian miRNA and RNAi pathways was divided into two parts, where first one presented here reviews components of the pathways and the second one reviews function and significance of the pathways.

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Renaissance of mammalian endogenous RNAi

Svoboda

2014

FEBS Letters

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a b s t r a c t RNA interference (RNAi) denotes sequence-specific mRNA degradation induced by long doublestranded RNA (dsRNA). RNAi is an ancient eukaryotic defense mechanism against viruses and mobile elements. In mammals, endogenous RNAi was outstripped during evolution by the current innate and acquired immunity. The RNAi apparatus, which remains essentially intact, serves mostly the microRNA pathway, which regulates endogenous gene expression. Remarkably, several recent publications brought the mammalian endogenous RNAi pathway back into the spotlight. Here, I will provide an up-to-date review of the mammalian endogenous RNAi pathway with a focus on its defensive role and overlaps with miRNA and piRNA pathways.

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The Canonical RNA Interference Pathway in Animals

Cited by 6 publications

References 0 publications

Production of small RNAs by mammalian Dicer

Production of small RNAs by mammalian Dicer

RNAi and miRNA pathways in mammals I – molecular mechanisms

Renaissance of mammalian endogenous RNAi

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